不同抗肿瘤治疗方法对肝癌肝移植术后复发转移的疗效比较

王媒西; 赵圆圆; 杨博; 魏来; 陈栋; 蒋继贫; 陈知水

doi:10.3969/j.issn.1674-7445.2021.03.008

不同抗肿瘤治疗方法对肝癌肝移植术后复发转移的疗效比较

doi: 10.3969/j.issn.1674-7445.2021.03.008

430030 武汉，华中科技大学同济医学院附属同济医院器官移植研究所器官移植教育部重点实验室国家卫生健康委员会器官移植重点实验室中国医学科学院器官移植重点实验室

基金项目:

国家自然科学基金 81770652

湖北省技术创新专项重大项目 2017ACA096

详细信息

作者简介:
王媒西，女，博士，住院医师，研究方向为肝移植，Email: 584913263@qq.com

通讯作者:
陈知水，男，博士，主任医师，研究方向为肝移植，Email: zschen@tjh.tjmu.edu.cn

中图分类号: R617, R735.7
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出版历程
- 收稿日期: 2021-01-03
- 网络出版日期: 2021-05-19
- 刊出日期: 2021-05-15

Comparison of clinical efficacy of different anti-tumor therapies for recurrence and metastasis after liver transplantation for liver cancer

Organ Transplantation Institute, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Key Laboratory of Organ Transplantation of Ministry of Education, Key Laboratory of Organ Transplantation of National Health Commission of China, Key Laboratory of Organ Transplantation of Chinese Academy of Medical Sciences, Wuhan 430030, China

More Information

Corresponding author: Chen Zhishui, Email: zschen@tjh.tjmu.edu.cn

摘要

摘要: 目的分析不同抗肿瘤治疗方法对原发性肝癌（肝癌）肝移植术后复发转移的疗效。方法回顾性分析145例肝癌肝移植受者的临床资料。分析肝癌肝移植受者术后总体生存情况及复发转移情况。比较不同抗肿瘤治疗方法治疗复发转移受者的效果。结果 65例受者（44.8%）发生了复发转移，中位复发时间为6个月。其中1例复发后再次行肝移植，因肠穿孔死亡；24例（37%）接受靶向药物治疗，中位带瘤生存期为22个月；11例（17%）接受放射治疗（放疗）或化学药物治疗（化疗），中位带瘤生存期为11个月；9例（14%）接受局部治疗（手术切除或射频消融），中位带瘤生存期为8个月；20例（31%）未接受抗肿瘤治疗，中位带瘤生存期为3个月。接受抗肿瘤治疗受者的带瘤生存期较未接受抗肿瘤治疗受者延长（P < 0.001）；接受靶向药物治疗受者的带瘤生存期较接受其他抗肿瘤治疗受者延长（P=0.03）；接受局部治疗和放、化疗受者的带瘤生存期较未接受抗肿瘤治疗受者延长（P=0.004）。结论对于肝癌肝移植术后复发转移受者，首选手术切除和射频消融。对于无法接受局部治疗的多灶性肿瘤，使用靶向药物治疗的受者带瘤生存期最长，放、化疗亦能延长复发转移受者的生存期。
- 原发性肝癌 /
- 肝移植 /
- 复发转移 /
- 靶向药物治疗 /
- 局部治疗 /
- 放射治疗 /
- 化学药物治疗 /
- 射频消融
Abstract: Objective To analyze the clinical efficacy of different anti-tumor therapies for recurrence and metastasis after liver transplantation for primary liver cancer (liver cancer). Methods Clinical data of 145 recipients undergoing liver transplantation for liver cancer were retrospectively analyzed. The overall survival and recurrence and metastasis after liver transplantation for liver cancer were analyzed. The clinical efficacy of different anti-tumor therapies for recipients with recurrence and metastasis were compared. Results Sixty-five recipients (44.8%) developed recurrence and metastasis. The median recurrence time was 6 months. Among them, 1 case underwent secondary liver transplantation after recurrence and died of intestinal perforation. Twenty-four recipients (37%) received targeted drug therapy with a median tumor-bearing survival of 22 months. Eleven recipients (17%) received radiotherapy or chemotherapy with a median tumor-bearing survival of 11 months. Nine recipients (14%) received local treatment (surgical resection or radiofrequency ablation), and the median tumor-bearing survival was 8 months. Twenty recipients (31%) abandoned anti-tumor therapy, and the median tumor-bearing survival was 3 months. The tumor-bearing survival of recipients receiving anti-tumor therapy was significantly longer than that of recipients without anti-tumor therapy (P < 0.001). The tumor-bearing survival of recipients receiving targeted drug therapy was significantly longer than that of those receiving other anti-tumor therapies (P=0.03). The tumor-bearing survival of recipients receiving local treatment, radiotherapy and chemotherapy was considerably longer than that of those who abandoned anti-tumor therapy (P=0.004). Conclusions Surgical resection and radiofrequency ablation are the optimal therapies for recipients with recurrence and metastasis after liver transplantation for liver cancer. For recipients with multi-focal tumors who fail to receive local treatment, those receiving targeted drug therapy obtain the longest survival. In addition, radiotherapy and chemotherapy can also prolong the survival of recipients with recurrence and metastasis.
- Primary liver cancer /
- Liver transplantation /
- Recurrence and metastasis /
- Targeted drug therapy /
- Local treatment /
- Radiotherapy /
- Chemotherapy /
- Radiofrequency ablation

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图 1 肝癌肝移植术后复发转移受者的生存分析

注：A图为接受抗肿瘤治疗与未接受抗肿瘤治疗受者的生存分析；B图为接受不同抗肿瘤治疗受者的生存分析。

Figure 1. Survival analysis of recipients with recurrence and metastasis after liver transplantation for liver cancer

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表 1 接受不同抗肿瘤治疗方法的受者的临床特征比较

Table 1. Comparison of clinical characteristics of recipients with different anti-tumor therapies

变量	靶向药物治疗（n=24）	其他抗肿瘤治疗（局部治疗、放疗及化疗）（n=20）	未接受抗肿瘤治疗（n=20）	P值
年龄[M（Q₂₅，Q₇₅），岁]	53（40, 58）	49（41, 55）	51（39, 54）	0.703
性别[n（%）]				0.374
男	21（88）	20（100）	19（95）
女	3（12）	0（0）	1（5）
原发病[n（%）]				0.154
乙肝后肝癌	20（83）	19（95）	20（100）
酒精性肝病后肝癌	1（4）	1（5）	0（0）
其他原因肝癌	3（12）	0（0）	0（0）
术前MELD^①评分[M（Q₂₅，Q₇₅），分]	7（5, 16）	6（4, 9）	9（4, 19）	0.425
术前AFP[M（Q₂₅，Q₇₅），ng/mL]	83（10, 10 512）	2 000（17, 10 144）	717（63, 20 931）	0.502
肿瘤数量[n（%）]				0.324
单发	14（58）	10（50）	5（25）
多发	10（42）	10（50）	15（75）
最大肿瘤直径[M（Q₂₅，Q₇₅），cm]	5（3, 9）	5（3, 8)	5（3, 10）	0.602
有血管侵犯[n（%）]	9（38）	11（55）	9（45）	0.230
米兰标准内[n（%）]	6（25）	7（35）	4（20）	0.528
杭州标准内[n（%）]	9（38）	8（40）	8（40）	0.981
术前抗肿瘤治疗[n（%）]				0.379
未治疗	6（25）	7（35）	9（45）
TACE或射频消融	18（75）	13（65）	11（55）
病理分化[n（%）]				0.649
高	2（8）	0（0）	0（0）
中	11（46）	7（35）	8（40）
低	10（42）	11（55）	9（45）
坏死	1（4）	2（10）	3（15）
术后复发时间[M（Q₂₅，Q₇₅），月]	6（3, 10）	6（3, 9）	5（2, 12）	0.962
复发转移部位[n（%）]
移植肝	6（25）	3（15）	1（5）	0.195
肺	8（33）	4（20）	3（15）	0.427
骨	0（0）	1（5）	2（10）	0.286
其他	10（42）	12（60）	14（70）	0.155
注：①MELD为终末期肝病模型。

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参考文献(32)

[1]	CHEN W, ZHENG R, BAADE PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132. DOI: 10.3322/caac.21338.
[2]	European Association for the Study of the Liver. EASL clinical practice guidelines: management of hepatocellular carcinoma[J]. J Hepatol, 2018, 69(1): 182-236. DOI: 10.1016/j.jhep.2018.03.019.
[3]	LLOVET JM, RICCI S, MAZZAFERRO V, et al. Sorafenib in advanced hepatocellular carcinoma[J]. N Engl J Med, 2008, 359(4): 378-390. DOI: 10.1056/NEJMoa0708857.
[4]	KUDO M, FINN RS, QIN S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial[J]. Lancet, 2018, 391(10126): 1163-1173. DOI: 10.1016/S0140-6736(18)30207-1.
[5]	KULIK L, EL-SERAG HB. Epidemiology and management of hepatocellular carcinoma[J]. Gastroenterology, 2019, 156(2): 477-491. DOI: 10.1053/j.gastro.2018.08.065.
[6]	RAHBARI NN, MEHRABI A, MOLLBERG NM, et al. Hepatocellular carcinoma: current management and perspectives for the future[J]. Ann Surg, 2011, 253(3): 453-469. DOI: 10.1097/SLA.0b013e31820d944f.
[7]	FORNER A, REIG M, BRUIX J. Hepatocellular carcinoma[J]. Lancet, 2018, 391(10127): 1301-1314. DOI: 10.1016/S0140-6736(18)30010-2.
[8]	KANNEGANTI M, MAHMUD N, KAPLAN DE, et al. Survival benefit of liver transplantation for hepatocellular carcinoma[J]. Transplantation, 2020, 104(1): 104-112. DOI: 10.1097/TP.0000000000002816.
[9]	AGOPIAN VG, HARLANDER-LOCKE M, ZARRINPAR A, et al. A novel prognostic nomogram accurately predicts hepatocellular carcinoma recurrence after liver transplantation: analysis of 865 consecutive liver transplant recipients[J]. J Am Coll Surg, 2015, 220(4): 416-427. DOI: 10.1016/j.jamcollsurg.2014.12.025.
[10]	ZIMMERMAN MA, GHOBRIAL RM, TONG MJ, et al. Recurrence of hepatocellular carcinoma following liver transplantation: a review of preoperative and postoperative prognostic indicators[J]. Arch Surg, 2008, 143(2): 182-188. DOI: 10.1001/archsurg.2007.39.
[11]	中国医师协会器官移植医师分会, 中华医学会器官移植学分会. 中国肝癌肝移植临床实践指南(2018版)[J]. 临床肝胆病杂志, 2019, 35(2): 275-280. DOI: 10.3969/j.issn.1001-5256.2019.02.008 Branch of Organ Transplant Physicians of Chinese Medical Doctor Association, Branch of Organ Transplantation of Chinese Medical Association. The Chinese clinical practice guideline on liver transplantation for hepatocellular carcinoma (2018 edition)[J]. J Clin Hepatol, 2019, 35(2): 275-280. DOI: 10.3969/j.issn.1001-5256.2019.02.008.
[12]	王征, 周俭. 中国肝癌肝移植现状及展望[J/CD]. 实用器官移植电子杂志, 2019, 7(1): 1-3. DOI:10.3969/j.issn.2095-5332.2019.01.001. WANG Z, ZHOU J. Current status and prospect of liver transplantation for hepatocellular carcinoma in China[J/CD]. Pract J Organ Transplant (Electr Vers), 2019, 7(1): 1-3. DOI:10.3969/j.issn.2095-5332.2019.01.001.
[13]	PARK JW, CHEN M, COLOMBO M, et al. Global patterns of hepatocellular carcinoma management from diagnosis to death: the BRIDGE study[J]. Liver Int, 2015, 35(9): 2155-2166. DOI: 10.1111/liv.12818.
[14]	陈晓, 蔡建强. 《原发性肝癌诊疗规范(2017年版)》解读[J/CD]. 肝癌电子杂志, 2017, 4(3): 1-5. DOI:10.3969/j.issn.2095-7815.2017.03.002. CHEN X, CAI JQ. Interpretation of diagnosis and treatment specification for primary liver cancer (2017 edition)[J/CD]. Electr J Liver Tumor, 2017, 4(3): 1-5. DOI:10.3969/j.issn.2095-7815.2017.03.002.
[15]	汪国营. 肝癌肝移植相关热点问题探讨[J]. 中山大学学报(医学科学版), 2021, 42(1): 17-23. WANG GY. Hot issues related to liver transplantation for hepatocellular carcinoma[J]. J Sun Yat-sen Univ (Med Sci), 2021, 42(1): 17-23.
[16]	BARAZANI Y, HIATT JR, TONG MJ, et al. Chronic viral hepatitis and hepatocellular carcinoma[J]. World J Surg, 2007, 31(6): 1243-1248. DOI: 10.1007/s00268-007-9041-3.
[17]	BODZIN AS, LUNSFORD KE, MARKOVIC D, et al. Predicting mortality in patients developing recurrent hepatocellular carcinoma after liver transplantation: impact of treatment modality and recurrence characteristics[J]. Ann Surg, 2017, 266(1): 118-125. DOI: 10.1097/SLA.0000000000001894.
[18]	DE'ANGELIS N, LANDI F, CARRA MC, et al. Managements of recurrent hepatocellular carcinoma after liver transplantation: a systematic review[J]. World J Gastroenterol, 2015, 21(39): 11185-11198. DOI: 10.3748/wjg.v21.i39.11185.
[19]	CHENG AL, KANG YK, CHEN Z, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase Ⅲ randomised, double-blind, placebo-controlled trial[J]. Lancet Oncol, 2009, 10(1): 25-34. DOI: 10.1016/S1470-2045(08)70285-7.
[20]	MARTIN RC 2ND, BRUENDERMAN E, COHN A, et al. Sorafenib use for recurrent hepatocellular cancer after resection or transplantation: observations from a US regional analysis of the GIDEON registry[J]. Am J Surg, 2017, 213(4): 688-695. DOI: 10.1016/j.amjsurg.2016.10.006.
[21]	TOMONARI T, SATO Y, TANI J, et al. Comparison of therapeutic outcomes of sorafenib and lenvatinib as primary treatments for hepatocellular carcinoma with a focus on molecular-targeted agent sequential therapy: a propensity score-matched analysis[J]. Hepatol Res, 2021, 51(4): 472-481. DOI: 10.1111/hepr.13597.
[22]	李凯. 复杂肝癌病例热消融治疗的策略和技巧[J]. 中山大学学报(医学科学版), 2019, 40(6): 814-820. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSYK201906003.htm LI K. Treatment skills of thermal ablation in complicated hepatocellular carcinoma cases[J]. J Sun Yat-sen Univ (Med Sci), 2019, 40(6): 814-820. https://www.cnki.com.cn/Article/CJFDTOTAL-ZSYK201906003.htm
[23]	史瑶平, 池嘉昌, 施东华, 等. 局部消融治疗术后单发复发肝细胞癌长期生存研究[J]. 中国实用外科杂志, 2020, 40(6): 710-714. DOI: 10.19538/j.cjps.issn1005-2208.2020.06.19. SHI YP, CHI JC, SHI DH, et al. Long-term survival of local ablation for single recurrent hepatocellular carcinoma after liver resection[J]. Chin J Pract Surg, 2020, 40(6): 710-714. DOI: 10.19538/j.cjps.issn1005-2208.2020.06.19.
[24]	徐肖静, 吴俊, 李惠, 等. 超声造影引导常规超声检查阴性复发性肝细胞性肝癌射频消融近期疗效分析[J]. 实用医学杂志, 2018, 34(3): 401-405. DOI: 10.3969/j.issn.1006-5725.2018.03.015. XU XJ, WU J, LI H, et al. Contrast-enhanced ultrasound guided radiofrequency ablation for conventional ultrasound negative recur-rent hepatocellular carcinoma: analysis of the recent therapeutic efficacy[J]. J Pract Med, 2018, 34(3): 401-405. DOI: 10.3969/j.issn.1006-5725.2018.03.015.
[25]	SAPISOCHIN G, GOLDARACENA N, ASTETE S, et al. Benefit of treating hepatocellular carcinoma recurrence after liver transplantation and analysis of prognostic factors for survival in a large Euro-American series[J]. Ann Surg Oncol, 2015, 22(7): 2286-2294. DOI: 10.1245/s10434-014-4273-6.
[26]	吴珺艺, 孙红成, 彭志海. 肝癌肝移植术后辅助化疗的临床意义及应用[J]. 国际外科学杂志, 2010, 37(2): 112-115. DOI: 10.3760/cma.j.issn.1673-4203.2010.02.013. WU JY, SUN HC, PENG ZH. Adjuvant chemotherapy in hepatocellular carcinoma after liver transplantation[J]. Int J Surg, 2010, 37(2): 112-115. DOI: 10.3760/cma.j.issn.1673-4203.2010.02.013.
[27]	WANG MX, CHEN D, ZHAO YY, et al. Role of selected criteria and preventive chemotherapy in tumor recurrence after liver transplantation[J]. Hepatobiliary Pancreat Dis Int, 2020, 19(4): 378-383. DOI: 10.1016/j.hbpd.2020.06.008.
[28]	曾昭冲. 肝癌立体定向放疗是值得探索的根治性方法[J]. 肝脏, 2020, 25(7): 665-667. https://www.cnki.com.cn/Article/CJFDTOTAL-ZUAN202007005.htm ZENG ZC. Stereotactic radiotherapy for hepatocellular carcinoma is a radical method worth exploring[J]. Chin Hepatol, 2020, 25(7): 665-667. https://www.cnki.com.cn/Article/CJFDTOTAL-ZUAN202007005.htm
[29]	YEUNG CSY, CHIANG CL, WONG NSM, et al. Palliative liver radiotherapy (RT) for symptomatic hepatocellular carcinoma (HCC)[J]. Sci Rep, 2020, 10(1): 1254. DOI: 10.1038/s41598-020-58108-1.
[30]	CHOLONGITAS E, MAMOU C, RODRÍGUEZ-CASTRO KI, et al. Mammalian target of rapamycin inhibitors are associated with lower rates of hepatocellular carcinoma recurrence after liver transplantation: a systematic review[J]. Transpl Int, 2014, 27(10): 1039-1049. DOI: 10.1111/tri.12372.
[31]	GRIGG SE, SARRI GL, GOW PJ, et al. Systematic review with Meta-analysis: sirolimus- or everolimus-based immunosuppression following liver transplantation for hepatocellular carcinoma[J]. Aliment Pharmacol Ther, 2019, 49(10): 1260-1273. DOI: 10.1111/apt.15253.
[32]	LING S, FENG T, ZHAN Q, et al. Sirolimus-based immunosuppression improves outcomes in liver transplantation recipients with hepatocellular carcinoma beyond the Hangzhou criteria[J]. Ann Transl Med, 2020, 8(4): 80. DOI: 10.21037/atm.2020.01.10.