经肝动脉化疗栓塞术联合射频消融治疗巴塞罗那B期原发性肝癌的效果及预后影响因素分析
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摘要
目的探讨经肝动脉化疗栓塞术(TACE)联合肝癌射频消融(RFA)治疗巴塞罗那(BCLC) B期原发性肝癌患者的疗效及其预后影响因素。方法选择2007年1月-2012年1月在首都医科大学附属北京佑安医院住院行TACE联合RFA治疗的BCLC-B期原发性肝癌患者154例。收集所有患者基线实验室及影像检查资料,通过门诊、住院或电话随访所有病例。采用KaplanMeier法绘制生存曲线,采用log-rank检验生存曲线,将单因素分析中P <0. 05的指标纳入多因素Cox回归分析。结果 154例BCLC-B期肝癌患者,中位生存期37个月,1、2、3、5年生存率分别为82. 5%、59. 7%、50. 6%和36. 1%。将患者按照BCLC-B期亚分期分为B1、B2、B3、B4期,B1期患者生存率明显高于B2～B4期,差异有统计学意义(χ~2=16. 881,P=0. 001); RFA后1个月达到完全消融、年龄<60岁、术前AFP <400 ng/ml、胆碱酯酶≥4000 U/L、TBil≤21μmol/L、Child-Pugh A级,肿瘤数目≤3个、肿瘤最大直径<3 cm组患者生存率分别高于不完全消融、年龄≥60岁、AFP≥400 ng/ml、胆碱酯酶<4000 U/L、TBil> 21μmol/L、ChildPugh B级、肿瘤数目> 3个、肿瘤最大直径> 5 cm组,差异均有统计学意义(χ~2=173. 002,P <0. 001;χ~2=6. 336,P=0. 012;χ~2=10. 765,P=0. 001;χ~2=6. 933,P=0. 008;χ~2=4. 624,P=0. 032;χ~2=5. 570,P=0. 018;χ~2=6. 761,P=0. 009;χ~2=7. 430,P=0.024)。Cox多因素回归分析显示消融评价[P <0. 001,比值比(OR)=21. 950,95%可信区间(95%CI):11. 817～40. 772]、ChildPugh分级(P=0. 002,OR=2. 190,95%CI:1. 329～3. 609)、AFP水平(P=0. 014,OR=1. 760,95%CI:1. 122～2. 760)、B期亚分期(P=0. 004,OR=2. 178,95%CI:1. 284～3. 694)是BCLC-B期肝癌患者RFA治疗后生存期的影响因素。结论 TACE联合RFA治疗BCLC-B期肝癌安全有效,不完全消融、AFP≥400 ng/ml、Child-Pugh B级、BCLC-B期亚分期越晚是影响BCLC-B期肝癌RFA治疗后生存期的独立危险因素。
Objective To investigate the clinical effect of transcatheter arterial chemoembolization( TACE) combined with radiofrequency ablation( RFA) in the treatment of Barcelona Clinical Liver Cancer( BCLC) stage B primary liver cancer and influencing factors for prognosis. Methods A total of 154 patients with BCLC stage B primary liver cancer who were admitted to Beijing YouAn Hospital,Capital Medical University,from January 2007 to January 2012 and underwent TACE combined with RFA were enrolled. Baseline laboratory data and imaging findings were collected for all patients,and all patients were followed up by the outpatient service,hospitalization,or telephone. The Kaplan-Meier method was used to plot survival curves and the log-rank test was used for the analysis of survival curves. The indicators with P < 0. 05 in the univariate analysis were included in multivariate Cox regression analysis. Results The 154 patients with BCLC stage B liver cancer had a median survival time of 37 months and the 1-,2-,3-,and 5-year survival rates were 82. 5%,59. 7%,50. 6%,and 36. 1%,respectively. The patients were divided into B1,B2,B3,and B4 groups according to the BCLC substage,and the B1 group had a significantly higher survival rate than the B2,B3,and B4 groups( χ~2= 16. 881,P = 0. 001). The patients with complete ablation at one month after RFA,an age of < 60 years,an alpha-fetoprotein( AFP) level of < 400 ng/ml,a cholinesterase( ChE) level of ≥4000 U/L,a total bilirubin( TBil) level of ≤21 μmol/L,a Child-Pugh class A disease,a number of tumors of ≤3,or a maximum tumor diameter of < 3 cm had a significantly higher survival rate than those with incomplete ablation( χ~2= 173. 002,P < 0. 001),an age of ≥60 years( χ~2= 6. 336,P = 0. 012),an AFP level of ≥400 ng/ml( χ~2= 10. 765,P = 0. 001),a ChE level of < 4000 U/L( χ~2= 6. 933,P =0. 008),a TBil level of > 21 μmol/L( χ~2= 4. 624,P = 0. 032),a Child-Pugh class B disease( χ~2= 5. 570,P = 0. 018),a number of tumors of > 3( χ~2= 6. 761,P = 0. 009),or a maximum tumor diameter of > 5 cm( χ~2= 7. 430,P = 0. 024). The multivariate Cox regression analysis showed that ablation assessment( odds ratio [OR]= 21. 950,95% confidence interval [CI]: 11. 817-40. 772,P < 0. 001),Child-Pugh class( OR = 2. 190,95% CI: 1. 329-3. 609,P = 0. 002),AFP level( OR = 1. 760,95% CI: 1. 122-2. 760,P = 0. 014),and BCLC B substage( OR = 2. 178,95% CI: 1. 284-3. 694,P = 0. 004) were influencing factors for survival time after RFA in patients with BCLC stage B liver cancer. Conclusion TACE combined with RFA is safe and effective in the treatment of BCLC stage B liver cancer.Incomplete ablation,a AFP level of ≥400 ng/ml,Child-Pugh class B,and late substage of BCLC stage B are independent risk factors for survival time after RFA in patients with BCLC stage B liver cancer.
Objective To investigate the clinical effect of transcatheter arterial chemoembolization( TACE) combined with radiofrequency ablation( RFA) in the treatment of Barcelona Clinical Liver Cancer( BCLC) stage B primary liver cancer and influencing factors for prognosis. Methods A total of 154 patients with BCLC stage B primary liver cancer who were admitted to Beijing YouAn Hospital,Capital Medical University,from January 2007 to January 2012 and underwent TACE combined with RFA were enrolled. Baseline laboratory data and imaging findings were collected for all patients,and all patients were followed up by the outpatient service,hospitalization,or telephone. The Kaplan-Meier method was used to plot survival curves and the log-rank test was used for the analysis of survival curves. The indicators with P < 0. 05 in the univariate analysis were included in multivariate Cox regression analysis. Results The 154 patients with BCLC stage B liver cancer had a median survival time of 37 months and the 1-,2-,3-,and 5-year survival rates were 82. 5%,59. 7%,50. 6%,and 36. 1%,respectively. The patients were divided into B1,B2,B3,and B4 groups according to the BCLC substage,and the B1 group had a significantly higher survival rate than the B2,B3,and B4 groups( χ~2= 16. 881,P = 0. 001). The patients with complete ablation at one month after RFA,an age of < 60 years,an alpha-fetoprotein( AFP) level of < 400 ng/ml,a cholinesterase( ChE) level of ≥4000 U/L,a total bilirubin( TBil) level of ≤21 μmol/L,a Child-Pugh class A disease,a number of tumors of ≤3,or a maximum tumor diameter of < 3 cm had a significantly higher survival rate than those with incomplete ablation( χ~2= 173. 002,P < 0. 001),an age of ≥60 years( χ~2= 6. 336,P = 0. 012),an AFP level of ≥400 ng/ml( χ~2= 10. 765,P = 0. 001),a ChE level of < 4000 U/L( χ~2= 6. 933,P =0. 008),a TBil level of > 21 μmol/L( χ~2= 4. 624,P = 0. 032),a Child-Pugh class B disease( χ~2= 5. 570,P = 0. 018),a number of tumors of > 3( χ~2= 6. 761,P = 0. 009),or a maximum tumor diameter of > 5 cm( χ~2= 7. 430,P = 0. 024). The multivariate Cox regression analysis showed that ablation assessment( odds ratio [OR]= 21. 950,95% confidence interval [CI]: 11. 817-40. 772,P < 0. 001),Child-Pugh class( OR = 2. 190,95% CI: 1. 329-3. 609,P = 0. 002),AFP level( OR = 1. 760,95% CI: 1. 122-2. 760,P = 0. 014),and BCLC B substage( OR = 2. 178,95% CI: 1. 284-3. 694,P = 0. 004) were influencing factors for survival time after RFA in patients with BCLC stage B liver cancer. Conclusion TACE combined with RFA is safe and effective in the treatment of BCLC stage B liver cancer.Incomplete ablation,a AFP level of ≥400 ng/ml,Child-Pugh class B,and late substage of BCLC stage B are independent risk factors for survival time after RFA in patients with BCLC stage B liver cancer.
引文
[1]European Association for the Study of the Liver,European Organisation for Research and Treatment of Cancer. EASLEORTC clinical practice guidelines:Management of hepatocellular carcinoma[J]. J Hepatol,2012,56(4):908-943.
[2]BRUIX J,SHERMAN M,American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma:An update[J]. Hepatology,2011,53(3):1020-1022.
[3]LI X. Short-and long-term efficacy of transarterial chemoembolization versus liver resection in treatment of patients with Barcelona stage B multiple hepatocellular carcinoma[J]. J Clin Hepatol,2017,33(7):1296-1300.(in Chinese)黎昕.经肝动脉化疗栓塞术与肝切除术治疗巴塞罗那B期多发性肝细胞癌的近远期效果比较[J].临床肝胆病杂志,2017,33(7):1296-1300.
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[5]National Health and Family Planning Commission of the People's Republic of China. Diagnosis,management,and treatment of hepatocellular carcinoma(V2017)[J]. J Clin Hepatol,2017,33(8):1419-1431.(in Chinese)中华人民共和国国家卫生和计划生育委员会.原发性肝癌诊疗规范(2017年版)[J].临床肝胆病杂志,2017,33(8):1419-1431.
[6]BOLONDI L,BURROUGHS A,DUFOUR JF,et al. Heterogeneity of patients with intermediate(BCLC B)Hepatocellular Carcinoma:Proposal for a subclassification to facilitate treatment decisions[J]. Semin Liver Dis,2012,32(4):348-359.
[7]BIOLATO M,GALLUSI G,IAVARONE M,et al. Prognostic ability of BCLC-B subclassification in patients with hepatocellular carcinoma undergoing transarterial chemoembolization[J].Ann Hepatol,2018,17(1):110-118.
[8]YANG B,ZHENG B,YANG M,et al. Liver resection versus transarterial chemoembolization for the initial treatment of Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma[J]. Hepatol Int,2018,12(5):417-428.
[9]LI YM,MA Z,CHEN H. Radiofrequency ablation for primary liver cancer[J/CD]. Chin J Hepatic Surg:Electronic Edition,2017,6(5):337-342.(in Chinese)李玉民,马臻,陈昊.原发性肝癌射频消融治疗[J/CD].中华肝脏外科手术学电子杂志,2017,6(5):337-342.
[10]YIN X,ZHANG L,WANG YH,et al. Transcatheter arterial chemoembolization combined with radiofrequency ablation delays tumor progression and prolongs overall survival in patients with intermediate(BCLC B)hepatocellular carcinoma[J]. BMC Cancer,2014,14:849.
[11]HIROOKA M,HIRAOKA A,OCHI H,et al. Transcatheter arterial chemoembolization with or without radiofrequency ablation:Outcomes in patients with Barcelona Clinic Liver Cancer Stage B hepatocellular carcinoma[J]. AJR Am J Roentgenol,2018,210(4):891-898.
[12]HA Y,SHIM JH,KIM SO,et al. Clinical appraisal of the recently proposed Barcelona Clinic Liver Cancer stage B subclassification by survival analysis[J]. J Gastroenterol Hepatol,2014,29(4):787-793.
[13]SCAFFARO LA,STELLA SF,ALVARES-DA-SILVA MR,et al. Survival rates according to barcelona clinic liver cancer sub-staging system after transarterial embolization for intermediate hepatocellular carcinoma[J]. World J Hepatol,2015,7(3):628-632.
[14]XU HX,LU MD,XIE XY,et al. Prognostic factors for longterm outcome after percutaneous thermal ablation for hepatocellular carcinoma:A survival analysis of 137 consecutive patients[J]. Clin Radiol,2005,60(9):1018-1025.
[15]YIN XY,XIE XY,LU MD,et al. Percutaneous thermal ablation of medium and large hepatocellular carcinoma:Long-term outcome and prognostic factors[J]. Cancer,2009,115(9):1914-1923.
[16]LI J,ZHU WL,KANG XX,et al. Prognostic factors and model of primary liver cancer treated with transcatheter arterial chemoembolization combined with radiofrequency ablation[J].Chin J Oncol,2017,39(10):787-791.(in Chinese)李靖,朱文良,康鑫鑫,等.经肝动脉化疗栓塞联合射频消融治疗原发性肝癌的预后影响因素及预测模型[J].中华肿瘤杂志,2017,39(10):787-791.
[17]HENG-JUN G,YAO-JUN Z,MIN-SHAN C,et al. Rationality and effectiveness of transarterial chemoembolization as an initial treatment for BCLC B stage HBV-related hepatocellular carcinoma[J]. Liver Int,2014,34(4):612-620.
[18]TAKADA H,KUROSAKI M,NAKANISHI H,et al. Impact of pre-sarcopenia in sorafenib treatment for advanced hepatocellular carcinoma[J]. PLo S One,2018,13(6):e0198812.
[19]GUO XD,SUN SS,LI WD,et al. Clinical features of patients with Barcelona Clinic Liver Cancer stage C primary liver cancer and related prognostic factors:An analysis of 140 cases[J].J Clin Hepatol,2018,34(7):1456-1461.(in Chinese)郭晓笛,孙莎莎,李文东,等. 140例BCLC分期C期原发性肝癌患者的临床特征及预后影响因素分析[J].临床肝胆病杂志,2018,34(7):1456-1461.
[20]XU XF,XING H,HAN J,et al. Risk factors,patterns,and outcomes of late recurrence after liver resection for hepatocellular carcinoma:A multicenter study from China[J]. JAMA Surg,2018.[Epub ahead of print]
[21]KIM CJ,KIM HJ,PARK JH,et al. Radiologic response to transcatheter hepatic arterial chemoembolization and clinical outcomes in patients with hepatocellular carcinoma[J]. Liver Int,2014,34(2):305-312.
[22]YIN L,LI H,LI AJ,et al. Partial hepatectomy vs. transcatheter arterial chemoembolization for resectable multiple hepatocellular carcinoma beyond Milan Criteria:A RCT[J]. J Hepatol,2014,61(1):82-88.
[23]ZHAO YN,ZHANG YQ,YE JZ,et al. Hepatic resection versus transarterial chemoembolization for patients with Barcelona Clinic Liver Cancer intermediate stage Child-Pugh A hepatocellular carcinoma[J]. Exp Ther Med,2016,12(6):3813-3819.
[24]DONADON M,CIMINO M,PROCOPIO F,et al. Potential role of cholinesterases to predict short-term outcome after hepatic resection for hepatocellular carcinoma[J]. Updates Surg,2013,65(1):11-18.
[25]YAO Q,BAO X,XUE R,et al. Prognostic value of immunoscore to identify mortality outcomes in adults with HBV-related primary hepatocellular carcinoma[J]. Medicine(Baltimore),2017,96(17):e6735.
[2]BRUIX J,SHERMAN M,American Association for the Study of Liver Diseases. Management of hepatocellular carcinoma:An update[J]. Hepatology,2011,53(3):1020-1022.
[3]LI X. Short-and long-term efficacy of transarterial chemoembolization versus liver resection in treatment of patients with Barcelona stage B multiple hepatocellular carcinoma[J]. J Clin Hepatol,2017,33(7):1296-1300.(in Chinese)黎昕.经肝动脉化疗栓塞术与肝切除术治疗巴塞罗那B期多发性肝细胞癌的近远期效果比较[J].临床肝胆病杂志,2017,33(7):1296-1300.
[4]LLOVET JM,PAVEL M,RIMOLA J,et al. Pilot study of living donor liver transplantation for patients with hepatocellular carcinoma exceeding Milan Criteria(Barcelona Clinic Liver Cancer extended criteria)[J]. Liver Transpl,2018,24(3):369-379.
[5]National Health and Family Planning Commission of the People's Republic of China. Diagnosis,management,and treatment of hepatocellular carcinoma(V2017)[J]. J Clin Hepatol,2017,33(8):1419-1431.(in Chinese)中华人民共和国国家卫生和计划生育委员会.原发性肝癌诊疗规范(2017年版)[J].临床肝胆病杂志,2017,33(8):1419-1431.
[6]BOLONDI L,BURROUGHS A,DUFOUR JF,et al. Heterogeneity of patients with intermediate(BCLC B)Hepatocellular Carcinoma:Proposal for a subclassification to facilitate treatment decisions[J]. Semin Liver Dis,2012,32(4):348-359.
[7]BIOLATO M,GALLUSI G,IAVARONE M,et al. Prognostic ability of BCLC-B subclassification in patients with hepatocellular carcinoma undergoing transarterial chemoembolization[J].Ann Hepatol,2018,17(1):110-118.
[8]YANG B,ZHENG B,YANG M,et al. Liver resection versus transarterial chemoembolization for the initial treatment of Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma[J]. Hepatol Int,2018,12(5):417-428.
[9]LI YM,MA Z,CHEN H. Radiofrequency ablation for primary liver cancer[J/CD]. Chin J Hepatic Surg:Electronic Edition,2017,6(5):337-342.(in Chinese)李玉民,马臻,陈昊.原发性肝癌射频消融治疗[J/CD].中华肝脏外科手术学电子杂志,2017,6(5):337-342.
[10]YIN X,ZHANG L,WANG YH,et al. Transcatheter arterial chemoembolization combined with radiofrequency ablation delays tumor progression and prolongs overall survival in patients with intermediate(BCLC B)hepatocellular carcinoma[J]. BMC Cancer,2014,14:849.
[11]HIROOKA M,HIRAOKA A,OCHI H,et al. Transcatheter arterial chemoembolization with or without radiofrequency ablation:Outcomes in patients with Barcelona Clinic Liver Cancer Stage B hepatocellular carcinoma[J]. AJR Am J Roentgenol,2018,210(4):891-898.
[12]HA Y,SHIM JH,KIM SO,et al. Clinical appraisal of the recently proposed Barcelona Clinic Liver Cancer stage B subclassification by survival analysis[J]. J Gastroenterol Hepatol,2014,29(4):787-793.
[13]SCAFFARO LA,STELLA SF,ALVARES-DA-SILVA MR,et al. Survival rates according to barcelona clinic liver cancer sub-staging system after transarterial embolization for intermediate hepatocellular carcinoma[J]. World J Hepatol,2015,7(3):628-632.
[14]XU HX,LU MD,XIE XY,et al. Prognostic factors for longterm outcome after percutaneous thermal ablation for hepatocellular carcinoma:A survival analysis of 137 consecutive patients[J]. Clin Radiol,2005,60(9):1018-1025.
[15]YIN XY,XIE XY,LU MD,et al. Percutaneous thermal ablation of medium and large hepatocellular carcinoma:Long-term outcome and prognostic factors[J]. Cancer,2009,115(9):1914-1923.
[16]LI J,ZHU WL,KANG XX,et al. Prognostic factors and model of primary liver cancer treated with transcatheter arterial chemoembolization combined with radiofrequency ablation[J].Chin J Oncol,2017,39(10):787-791.(in Chinese)李靖,朱文良,康鑫鑫,等.经肝动脉化疗栓塞联合射频消融治疗原发性肝癌的预后影响因素及预测模型[J].中华肿瘤杂志,2017,39(10):787-791.
[17]HENG-JUN G,YAO-JUN Z,MIN-SHAN C,et al. Rationality and effectiveness of transarterial chemoembolization as an initial treatment for BCLC B stage HBV-related hepatocellular carcinoma[J]. Liver Int,2014,34(4):612-620.
[18]TAKADA H,KUROSAKI M,NAKANISHI H,et al. Impact of pre-sarcopenia in sorafenib treatment for advanced hepatocellular carcinoma[J]. PLo S One,2018,13(6):e0198812.
[19]GUO XD,SUN SS,LI WD,et al. Clinical features of patients with Barcelona Clinic Liver Cancer stage C primary liver cancer and related prognostic factors:An analysis of 140 cases[J].J Clin Hepatol,2018,34(7):1456-1461.(in Chinese)郭晓笛,孙莎莎,李文东,等. 140例BCLC分期C期原发性肝癌患者的临床特征及预后影响因素分析[J].临床肝胆病杂志,2018,34(7):1456-1461.
[20]XU XF,XING H,HAN J,et al. Risk factors,patterns,and outcomes of late recurrence after liver resection for hepatocellular carcinoma:A multicenter study from China[J]. JAMA Surg,2018.[Epub ahead of print]
[21]KIM CJ,KIM HJ,PARK JH,et al. Radiologic response to transcatheter hepatic arterial chemoembolization and clinical outcomes in patients with hepatocellular carcinoma[J]. Liver Int,2014,34(2):305-312.
[22]YIN L,LI H,LI AJ,et al. Partial hepatectomy vs. transcatheter arterial chemoembolization for resectable multiple hepatocellular carcinoma beyond Milan Criteria:A RCT[J]. J Hepatol,2014,61(1):82-88.
[23]ZHAO YN,ZHANG YQ,YE JZ,et al. Hepatic resection versus transarterial chemoembolization for patients with Barcelona Clinic Liver Cancer intermediate stage Child-Pugh A hepatocellular carcinoma[J]. Exp Ther Med,2016,12(6):3813-3819.
[24]DONADON M,CIMINO M,PROCOPIO F,et al. Potential role of cholinesterases to predict short-term outcome after hepatic resection for hepatocellular carcinoma[J]. Updates Surg,2013,65(1):11-18.
[25]YAO Q,BAO X,XUE R,et al. Prognostic value of immunoscore to identify mortality outcomes in adults with HBV-related primary hepatocellular carcinoma[J]. Medicine(Baltimore),2017,96(17):e6735.