Transarterial chemoembolization for inoperable,early stage hepatocellular carcinoma in patients with Child-Pugh grade A and B: results of a comparative study in 96 Chinese patients

OBJECTIVE: The efficacy of transarterial chemoembolization (TACE) in prolongation of survival is controversial. We conducted a comparative study to determine whether TACE treatment had any survival benefit for patients with unresectable hepatocellular carcinoma (HCC) and with relatively preserved liver function. METHODS: In all, 96 patients with unresectable HCC of Okuda stage I or II and Child-Pugh grade A or B were recruited. A total of 80 patients (group 1) who received TACE were compared to 16 patients (group 2) who were treated conservatively. RESULTS: The median survival time of group 1 patients was significantly longer than that of group 2 patients (31.2 vs 14.1 months respectively, p = 0.0126). The cumulative survival rates at 6 months, 1 yr, 2 yr, 3 yr, and 4 yr of group 1 compared to group 2 were as follows: 93.8% versus 62.5% (p = 0.002); 86.3% versus 62.5% (p = 0.023); 78.8% versus 50% (p = 0.017); 57.5% versus 50% (p = ns); and 51.3% versus 43.8% (p = ns), respectively. Tumor response was observed in 28% of patients receiving TACE. Patients with higher pretreatment albumin levels, lower pretreatment alpha-fetoprotein levels, and Okuda stage I disease were associated with a favorable response to TACE. CONCLUSION: TACE treatment improved survival in patients with unresectable HCC in the early stages and with relatively preserved liver function.     

Transcatheter arterial chemoembolization therapy for patients with hepatocellular carcinoma: a case-controlled study.

BACKGROUND & AIMS: Transcatheter arterial chemoembolization (TACE) currently is used as a palliative treatment for patients with unresectable hepatocellular carcinoma (HCC), but its efficacy still is debated. Our aim was to assess the impact of TACE on patient survival and to identify prognostic factors for survival. METHODS: Fifty-six cirrhotic patients with unresectable HCC undergoing at least 1 course of TACE were matched 1:1 for sex, age (in 5-year periods), parameters of Child-Pugh score, Okuda stage, and tumor type with a control group who had received only supportive care. RESULTS: The 2 groups were comparable for cause of cirrhosis, alpha-fetoprotein serum levels, and Cancer of the Liver Italian Program (CLIP) score. The 56 patients in the TACE group received a total of 123 treatment courses. The median follow-up period was 16 months (range, 1-67 mo) in the TACE group and 5 months (range, 1-77 mo) in the supportive care group. Survival rates at 12, 24, and 30 months in patients receiving TACE were 74.3%, 52.1%, and 38.8%, respectively, with a median survival time of 25 months, whereas in supportive care patients the rates were 39.4%, 25.4%, and 19%, respectively, with a median survival time of 7 months (P = .0004). At univariate analysis, TACE, tumor type, presence of ascites, alpha-fetoprotein serum level, CLIP score, and Okuda stage were associated significantly with survival. Only TACE and CLIP score proved to be independent predictors of survival at multivariate analysis. CONCLUSIONS: TACE is an effective therapeutic option for cirrhotic patients with unresectable HCC and a CLIP score of 3 or less.     

Therapeutic effects and prognostic factors in three-dimensional conformal radiotherapy combined with transcatheter arterial chemoembolization for hepatocellular carcinoma

AIM: To evaluate the therapeutic efficacy of threedimensional conformal radiotherapy (3D-CRT) combined with transcatheter arterial chernoembolization (TACE) on the patients with hepatocellular carcinoma (HCC).METHODS: Between 1998 and 2001, 94 patients with HCC received 3D-CRT combined with TACE. A total 63 patients had a Okuda stage Ⅰ lesion and 31 patients had stage Ⅱ. The median tumor size was 10.7 cm (range 3.0-18 cm), and liver drrhosis was present in all the patients. There were 43 cases of class A and 51 dass B. TACE was performed using lipiodol,5-fluorouracil, cisplatin, doxorubicin hydrochloride and mitomycin, followed by gelatin sponge cubes. Fifty-nine patients received TACE only one time, while the others 2 to 3 times. 3D-CRT was started 3-4 wk after TACE. All patients were irradiated with a stereotactic body frame and received 4-8 Gy single high-dose radiation for 8-12 times at the isocenter during a period of 17-26 d (median 22 d).RESULTS: The median follow-up was 37 mo (range 10-48 mo) after diagnosis. The response rate was 90.5%. The overallsurvival rate at 1-, 2-, and 3- year was 93.6%, 53.8% and 26.0% respectively, with the median survival of 25 too. On univariate analysis, age (P=-0.026), Child-Pugh classification for cirrhosis of liver (P=0.010), Okuda stage (P=-0.026),tumor size (P=0.000), tumor type (P=0.029), albuminemia (P=0.035), and radiation dose (P=0.000) proved to be significant factors for survival. On multivariate analysis,age (P=-0.024), radiation dose(P=-0.001), and tumor size (P=0.000) were the significant factors.CONCLUSION: 3D-CRT combined with TACE is an effective and feasible approach for HCC. Age, radiation dose and tumor size were found to be significant prognostic factors for survival of patients with HCC treated by 3D-CRT combined with TACE. Further study for HCC is needed to improve the treatment efficacy.     

Local radiotherapy as a complement to incomplete transcatheter arterial chemoembolization in locally advanced hepatocellular carcinoma.

PURPOSE: In order to determine the effect of additional radiotherapy (RT) after an incomplete transcatheter arterial chemoembolization (TACE) in an unresectable hepatocellular carcinoma (HCC), the treatment results of patients receiving TACE plus RT were analyzed and compared with those treated with TACE alone. MATERIALS AND METHODS: One hundred and five patients with an unresectable HCC were treated with TACE from January 1992 to December 2002. In 73 of these patients, the TACE was incomplete. Among them, TACE was repeatedly performed in 35 patients (TACE group), and the remaining 38 patients were also treated with local RT (TACERT group). The patients were either in stage III or IVa, Eastern Cooperative Oncology Group 2 or less, and Child-Pugh class A or B. The average frequency of TACE prior to RT was 2 and the RT was started within 7-10 days after the TACE. RESULTS: The 2-year survival rate was significantly higher in the TACERT than in the TACE group (36.8 % vs. 14.3%, P=0.001). According to the tumor size, the 2-year survival rates in the TACERT and TACE groups were 63% vs. 42% in 5-7 cm (P=0.22), 50% vs. 0% in 8-10 cm (P=0.03), and 17% vs. 0% in larger than 10 cm (P=0.0002) respectively. CONCLUSION: There was a significantly improved survival rate in the TACERT group of unresectable HCC patients than in the TACE group, particularly in case of tumors > or =8 cm in diameter. Therefore, RT in addition to TACE is strongly recommended for patients with an unresectable HCC.     

mRECIST应答对经肝动脉化疗栓塞术治疗不可切除肝细胞癌患者预后的预测价值

目的探讨实体瘤疗效评价标准(mRECIST)应答对经肝动脉化疗栓塞术(TACE)治疗的不可切除肝细胞癌的预后价值。方法回顾性纳入2010年1月—2014年12月在空军军医大学第一附属医院消化介入科行TACE治疗连续的不可切除肝细胞癌患者190例。应用mRECIST标准评估TACE术后影像学应答,将肿瘤完全缓解(CR)和部分缓解(PR)患者定义为有应答组(n=89),将疾病进展(PD)和疾病稳定(SD)定义为无应答组(n=101)。采用Kaplan-Meier法计算中位生存时间,log-rank检验进行组间比较。利用Cox回归进行预后影响因素分析。结果根据mRECIST标准,CR、PR、SD和PD的患者分别有39(20.5%)例、50(26.3%)例、67(35.3%)例和34(17.9%)例。总人群的mRECIST客观应答率为46.8%。应答组的生存期明显高于无应答组,中位生存时间分别为29.9(95%CI:25.0~34.8)个月和7.5(95%CI:5.7~9.3)个月(P<0.001)。多因素分析结果显示,mRECIST应答(HR=2.02,P<0.001)、乙型肝炎(HR=4.03,P<0.001)和门静脉侵犯(HR=2.12,P=0.008)是影响患者生存的独立危险因素。结论mRECIST应答对经TACE治疗的不可切除肝细胞癌患者的预后具有一定的预测价值。     

Supportive treatment, resection and transcatheter arterial chemoembolization in resectable hepatocellular carcinoma: an analysis of survival in 419 patients.

OBJECTIVE AND DESIGN: Both surgical resection and transcatheter arterial chemoembolization (TACE) are effective treatments for hepatocellular carcinoma (HCC). Few reports have compared the different treatment modalities for resectable HCC based on clinically matched groups. The aim of this study was to compare the survival rate after surgery, TACE or supportive treatment in resectable HCC patients, and also in elderly patients (> or = 70 y/o). METHODS: From 1984 to 1993, 419 consecutive patients with resectable HCC were included in this study. Of these, 311 (74%) underwent resection of tumours and 46 (11%) refused operation, opting instead for TACE. The remaining 62 (15%) who refused both methods of treatment were given supportive care. Univariate and multivariate analyses for prognostic factors and the 5-year survival rate among the groups were studied. RESULTS: Both surgical resection and TACE groups had a better 5-year survival rate than the supportive treatment group (43% and 34% vs. 7%). There was no difference in survival between the surgery and TACE groups. However, the 5-year survival rate was 11% in TACE and 41% in the surgical group when the patients were > or = 70. In multivariate analysis, female sex (P = 0.0466), tumour size < or = 3 cm (P = 0.0001), alpha-fetoprotein (AFP) < 400 U/l (P = 0.0036), single tumour (P = 0.0474), serum creatinine < or = 1.5 mg/dl (P = 0.0006) and alkaline phosphatase (AP) < or = 100 U/l (P = 0.0007) are associated with good prognosis for resectable HCC. CONCLUSION: TACE is an alternative for resectable HCC. Tumour size, tumour number, AFP level, renal function, AP level and female sex are prognostic factors. In elderly people, TACE must be used prudently and has a worse prognosis.     

Transcatheter Arterial Chemoembolization Therapy for Patients With Unresectable Hepatocellular Carcinoma

Background:

Although transcatheter arterial chemoembolization (TACE) has been widely used as a palliative treatment for unresectable hepatocellular carcinoma (HCC), its actual efficacy and prognostic usefulness have not been clarified in past studies.

Objectives:

The aim of the study is to investigate the efficacy, complications, and prognostic factors of the TACE in unresectable HCC patients.

Patients and Methods:

Thirty-two patients with unresectable HCC were treated with TACE. The procedure was performed with a combination of Lipiodol, doxorubicin, and cytomycin followed by gelatin-sponge particles embolization. CT-scan imaging and liver function tests (AST, ALT, ALP, BIL, and PT) were performed before and after the TACE. All patients were followed-up for 6-months.

Results:

Of all patients, 1 and 11 patients respectively, exhibited a complete response (CR) and a partial response (PR) (response rate, CR+PR, 44%). Data have shown that tumor size, number of lesions and number of involved segments are significantly reduced after the TACE performance (P < 0.05). No significant clinical adverse effect was observed in patients after the intervention. Also, liver function tests including AST, ALT, ALP, BIL, and PT did not significantly differ before and after the intervention (P > 0.05). The 6-month cumulative survival rates of the 32 patients were 78.1 %, respectively. Univariate analysis showed that survival correlated significantly with the following factors: tumor size; ≥ 8 cm versus < 8 cm (P < 0.010), serum ALP level; < 300 versus ≥ 300 (P < 0.043), and number of liver involved segments; < 2 versus ≥ 2 (P < 0.020).

Conclusions:

We showed that in treatment of patients with unresectable hepatocellular carcinoma, TACE significantly improved the disease and the overall survival rate. Also, we introduce the tumor size, serum ALP level, and number of liver involved segments as prognostic factors of the procedure. Finally, TACE can be recommended as the initial treatment for unresectable HCC patients.     

Comparative effectiveness of traditional chemoembolization with or without sorafenib for hepatocellular carcinoma

AIM: To compare the overall survival (OS) and progression-free survival (PFS) with associated adverse events (AE) in patients with unresectable hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) + sorafenib vs TACE alone. METHODS: In this retrospective cohort study we collected data on all consecutive patients with a diagnosis of unresectable HCC between 2007 and 2011 who had been treated with TACE + sorafenib or TACE alone. We hypothesized that the combination therapy is superior to TACE alone in improving the survival in these patients. Data extracted included patient’s demographics, etiology of liver disease, histology of HCC, stage of liver disease with respect to model of end stage liverdisease score and Child-Turcotte-Pugh (CTP) classification and Barcelona Clinic Liver Cancer (BCLC) staging for HCC. Computed tomography scan findings, alpha fetoprotein levels, number of treatments and related AE were also recorded and analyzed. RESULTS: Of the 43 patients who met inclusion criteria, 13 were treated with TACE + sorafenib and 30 with TACE alone. There was no significant difference in median survival: 20.6 mo (95%CI: 13.4-38.4) for the TACE + sorafenib and 18.3 mo (95%CI: 11.8-32.9) for the TACE alone (P = 0.72). There were also no statistically significant differences between groups in OS (HR = 0.82, 95%CI: 0.38-1.77; P = 0.61), PFS (HR = 0.93, 95%CI: 0.45-1.89; P = 0.83), and treatment-related toxicities (P = 0.554). CTP classification and BCLC staging for HCC were statistically significant (P = 0.001, P = 0.04 respectively) in predicting the survival in patients with HCC. The common AE observed were abdominal pain, nausea, vomiting and mild elevation of liver enzymes. CONCLUSION: Combination therapy with TACE + sorafenib is safe and equally effective as TACE alone in patients with unresectable HCC. CTP classification and BCLC staging were the significant predictors of survival. Future trials with large number of patients are needed to further validate this observation.     

Transarterial chemoembolization in Barcelona Clinic Liver Cancer Stage 0/A hepatocellular carcinoma

AIM:To evaluate the clinical characteristics of patients with Barcelona Clinic Liver Cancer(BCLC)stage 0 and A hepatocellular carcinoma(HCC)after transarterial chemoembolization(TACE).METHODS:Between January 2001 and September2011,129 patients with BCLC stage 0 and stage A HCC who underwent TACE were retrospectively enrolled.Patient characteristics,routine computed tomography and TACE findings,survival time and 1-,5-,and 10-year survival rates,risk factors for mortality,and survival rates according to the number of risk factors were assessed.RESULTS:The mean size of HCC tumors was 2.4±1.1 cm,and the mean number of TACE procedures performed was 2.5±2.1.The mean overall survival time and 1-,5-,and 10-year survival rates were 80.6±4.9 mo and 91%,63%and 49%,respectively.In the Cox regression analysis,a Child-Pugh score>5(P=0.005,OR=3.86),presence of arterio-venous shunt(P=0.032,OR=4.41),amount of lipiodol used(>7 mL;P=0.013,OR=3.51),and female gender(P=0.008,OR=3.47)were risk factors for mortality.The 1-,5-,and 10-year survival rates according to the number of risk factors present were 96%,87%and 87%(no risk factors),89%,65%,and 35%(1 risk factor),96%,48%and unavailable(2 risk factors),and 63%,17%,and 0%(3 risk factors),respectively(P<0.001).CONCLUSION:TACE may be used as curative-intent therapy in patients with BCLC stage 0 and stage A HCC.The Child-Pugh score,arterio-venous shunt,amount of lipiodol used,and gender were related to mortality after TACE.     

经动脉化学栓塞和经皮冷冻序贯治疗肝细胞癌

目的 评价经动脉化学栓塞(TACE)和经皮冷冻序贯治疗无法切除的肝细胞肝癌(HCC)的疗效.方法 将420例无法手术切除的HCC患者分为TACE-冷冻序贯治疗组290例(序贯组)和单纯冷冻组130例(冷冻组).TACE按常规操作,术后2～4周行经皮冷冻治疗.1个月及以后每2～3个月随访1次,包括肝脏超声和(或)腹部CT,并检测血清甲胎蛋白(AFP).结果 平均随访(42±17)个月(范围24～70个月),所有患者消融灶局部复发率为17%,序贯组和冷冻组分别为11%和24%(P=0.001).1、2、3、4和5年平均存活率分别为72%、57%、47%、39%和31%.序贯组1年和2年存活率(71%和61%)与冷冻组(73%和54%)相似(P值分别=0.69和0.147);而4年和5年存活率,序贯组(49%和39%)高于冷冻组(21%和23%,P=0.001).序贯组有18例肿瘤直径＞5cm的患者存活逾5年,而冷冻组无一例.全组并发症发生率为24%,序贯组和冷冻组分别为21%和26%(P=0.06).冷冻组肝出血的发生率显著高于序贯组(P=0.02),且有2例发生肝破裂.结论 冷冻治疗前先行TACE能提高冷冻消融的疗效,减少其并发症,特别是肝出血.TACE和冷冻序贯疗法可能是治疗不能切除性HCC,特别是大肝癌的较好方法 .