经导管肝动脉化疗栓塞术联合微波消融用于复发性肝癌的预后及其相关预测因素分析

朱献忠; 张献南; 王琴; 周伶

doi:10.16766/j.cnki.issn.1674-4152.001774

经导管肝动脉化疗栓塞术联合微波消融用于复发性肝癌的预后及其相关预测因素分析

doi: 10.16766/j.cnki.issn.1674-4152.001774

浙江金华广福医院超声医学科，浙江金华 321000

基金项目:

浙江省医药卫生科技计划项目 2020PY085

金华市科技计划项目 2018-3-001C

详细信息

通讯作者:
朱献忠，E-mail：zhuxzdoc@163.com

中图分类号: R735.7 R730.5
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出版历程
- 收稿日期: 2020-03-18
- 网络出版日期: 2022-02-19

Prognosis of recurrent hepatocellular carcinoma patients after TACE combined with microwave ablation and analysis of prognosis-related predictive factors

Department of Ultrasound Medicine, Jinhua Guangfu Hospital, Jinhua, Zhejiang 321000, China

摘要

摘要: 目的探讨经导管肝动脉化疗栓塞术(transcatheter arterial chemoembolization，TACE)联合微波消融(microwave ablation，MWA)治疗复发性肝癌患者的预后及其相关因素，构建总生存率预测列线图。方法回顾性纳入2015年1月—2017年1月于浙江金华广福医院行TACE-MWA治疗的82例复发性肝癌患者的临床资料，根据预后分为进展组、无进展组、存活组、死亡组。记录患者病情进展和生存情况，分析二者的影响因素，建立列线图预测模型。结果患者治疗后2年总生存率为68.29%，无进展生存率为36.59%；进展组术前血清甲胎蛋白(AFP)水平高于无进展组，肿瘤数目和最大肿瘤直径均大于无进展组(均P < 0.05)；死亡组最大肿瘤直径大于存活组，肿瘤近肝门 < 2 cm例数和术前AFP水平均高于存活组，2组Child-Pugh、BCLC分级例数分布差异有统计学意义(均P < 0.05)；术前AFP水平、肿瘤数目、最大肿瘤直径(HR=1.026、51.487、2.463，P=0.024、0.047、0.016)为患者无进展生存危险因素；术前AFP水平、最大肿瘤直径、肿瘤近肝门 < 2 cm(HR=1.012、1.189、8.479，P=0.002、0.011、0.021)为患者总生存率危险因素；总生存率列线图一致性指数为0.919(95% CI：0.885~0.946)。结论肿瘤数目、大小、位置等因素对TACE-MWA治疗后复发性肝癌患者无进展生存和总体生存具有一定预测意义。
- 经导管肝动脉化疗栓塞术 /
- 微波消融 /
- 肝癌 /
- 总生存率
Abstract: Objective To explore the prognosis of recurrent hepatocellular carcinoma patients after transcatheter arterial chemoembolisation (TACE) combined with microwave ablation (MWA) and its related factors, constructing a prognostic nomogram concerning overall survival. Methods Retrospective analysis was performed on clinical data from recurrent hepatocellular carcinoma patients (82 cases) treated by TACE-MWA in our hospital from January 2015 to January 2017. The patients were divided into progress, non-progress, survival, and death groups depending on disease progression and survival. The progression and survival situation during 2 years of follow-up were recorded, and the related factors for both were analysed. A prognostic nomogram was then constructed. Results The overall survival of patients in the two years after TACE-MWA was 68.29%, and the progression-free survival rate was 36.59%. The preoperative AFP level, tumour number, and largest tumour diameter in the progress group were higher than those in the non-progress group (all P < 0.05). The largest tumour diameter, cases with tumour close to hepatic hilum < 2 cm, and preoperative AFP level in the death group were higher than those in the survival group (all P < 0.05). Statistical differences were observed between the two groups in terms of Child-Pugh classification and BCLC classification (all P < 0.05). The preoperative AFP level, tumour number, and largest tumour diameter (HR=1.026, 51.487, 2.463; P=0.024, 0.047, 0.016, respectively) were the risk factors of recurrent hepatocellular carcinoma patients' progression-free survival. Preoperative AFP level, largest tumour diameter, and tumour proximity to hepatic hilum < 2 cm (HR=1.012, 1.189, 8.479; P=0.002, 0.011, 0.021, respectively) were the risk factors of recurrent hepatocellular carcinoma patients' overall survival. The consistency index for predicting patients' overall survival in two years was 0.919 (95% CI: 0.885-0.946). Conclusion Emphasising on factors such as tumour number, size, and location has certain meaning for predicting the progression-free survival and overall survival of hepatocellular carcinoma patients after TACE-MWA.
- Transcatheter arterial chemoembolization /
- Microwave ablation /
- Hepatocellular carcinoma /
- Overall survival

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图 1 预测复发性肝癌患者总体生存的列线图模型

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表 1 无进展组和进展组复发性肝癌患者资料比较

组别	例数	年龄(x±s，岁)	性别[例(%)]		术前AFP水平(x±s，μg/L)	肿瘤数目(x±s，个)	肝硬化[例(%)]	门脉癌栓[例(%)]	最大肿瘤直径(x±s，mm)	肿瘤近肝门 < 2 cm[例(%)]
组别	例数	年龄(x±s，岁)	男性	女性	术前AFP水平(x±s，μg/L)	肿瘤数目(x±s，个)	肝硬化[例(%)]	门脉癌栓[例(%)]	最大肿瘤直径(x±s，mm)	肿瘤近肝门 < 2 cm[例(%)]
无进展组	30	57.52±13.33	26(86.67)	4(13.33)	288.78±92.09	1.55±0.48	27(90.00)	2(6.67)	24.64±5.57	11(36.67)
进展组	52	58.39±12.71	44(84.62)	8(15.38)	483.65±124.28	2.41±0.62	48(92.31)	5(9.62)	35.94±7.35	13(25.00)
统计量		-0.293^a	0.064^b		-7.478^a	-6.544^a	0.130^b	0.212^b	-7.292^a	1.251^b
P值		0.770	0.800		＜0.001	＜0.001	0.719	0.645	＜0.001	0.263

组别	例数		Child-Pugh[例(%)]		BCLC分级[例(%)]			ALT(x±s，U/L)	AST(x±s，U/L)	肿瘤位于特殊部位[例(%)]
组别	例数		A级	B级	A期	B期	C期	ALT(x±s，U/L)	AST(x±s，U/L)	肿瘤位于特殊部位[例(%)]
无进展组	30		13(43.33)	17(56.67)	11(36.67)	8(26.67)	11(36.67)	144.38±27.65	118.55±23.41	16(53.33)
进展组	52		21(40.38)	31(59.62)	19(36.54)	21(40.38)	12(23.08)	157.86±30.90	129.46±24.62	35(67.31)
统计量			0.068^b		-0.681^c			-1.975^a	-1.967^a	1.580^b
P值			0.794		0.496			0.052	0.053	0.209

组别	例数	肿瘤边缘不规则[例(%)]	淋巴结转移[例(%)]	TBIL(x±s，μmol/L)	病因[例(%)]				吸烟[例(%)]	饮酒[例(%)]
组别	例数	肿瘤边缘不规则[例(%)]	淋巴结转移[例(%)]	TBIL(x±s，μmol/L)	HBsAg阳性	丙肝抗体	酒精性肝病	其他	吸烟[例(%)]	饮酒[例(%)]
无进展组	30	6(20.00)	2(6.67)	79.03±16.45	25(83.33)	2(6.67)	1(3.33)	2(6.67)	5(16.67)	2(6.67)
进展组	52	11(21.15)	3(5.77)	82.53±17.69	41(78.85)	4(7.69)	4(7.69)	3(5.77)	8(15.38)	3(5.77)
统计量		0.015^b	0.027^b	-0.885^a	-0.467^b				0.023^b	0.027^b
P值		0.901	0.870	0.379	0.641				0.878	0.870
注：^a为t值，^b为χ²值，^c为Z值；AFP为甲胎蛋白；ALT为谷丙转氨酶；AST为谷草转氨酶；TBIL为总胆红素；HBsAg为乙肝表面抗原；BCLC为巴塞罗那临床肝癌分期。

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表 2 复发性肝癌患者无进展生存相关因素COX回归分析

因素	B	SE	Wald χ²	P值	HR值	95% CI
术前AFP水平	0.026	0.011	5.099	0.024	1.026	1.003~1.049
肿瘤数目	3.941	1.982	3.953	0.047	51.487	1.058~2 505.958
最大肿瘤直径	0.902	0.372	5.859	0.016	2.463	1.187~5.112

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表 3 存活组和死亡组复发性肝癌患者资料比较

组别	例数	年龄(x±s，岁)	性别[例(%)]		术前AFP水平(x±s，μg/L)	肿瘤数目(x±s，个)	肝硬化[例(%)]	门脉癌栓[例(%)]	最大肿瘤直径(x±s，mm)	肿瘤近肝门 < 2 cm[例(%)]
组别	例数	年龄(x±s，岁)	男性	女性	术前AFP水平(x±s，μg/L)	肿瘤数目(x±s，个)	肝硬化[例(%)]	门脉癌栓[例(%)]	最大肿瘤直径(x±s，mm)	肿瘤近肝门 < 2 cm[例(%)]
存活组	56	54.78±15.63	49(87.50)	7(12.50)	319.58±106.47	1.73±0.65	50(89.29)	3(5.36)	25.24±6.68	12(21.43)
死亡组	26	56.83±14.28	21(80.77)	5(19.23)	490.24±111.62	2.04±0.72	25(96.15)	4(15.38)	35.43±5.78	12(46.15)
统计量		-0.568^a	0.644^b		-6.652^a	-1.942^a	1.072^b	2.287^b	-6.696^a	5.243^b
P值		0.572	0.422		< 0.001	0.056	0.300	0.130	< 0.001	0.022

组别	例数		Child-Pugh[例(%)]		BCLC分级[例(%)]			ALT(x±s，U/L)	AST(x±s，U/L)	肿瘤位于特殊部位[例(%)]
组别	例数		A级	B级	A期	B期	C期	ALT(x±s，U/L)	AST(x±s，U/L)	肿瘤位于特殊部位[例(%)]
存活组	56		19(33.93)	37(66.07)	25(44.64)	18(32.14)	13(23.21)	148.95±28.36	124.48±24.83	38(67.86)
死亡组	26		15(57.69)	11(42.31)	5(19.23)	11(42.31)	10(38.46)	161.18±24.72	130.77±22.69	13(50.00)
统计量			4.131^b		-2.156^c			-1.889^a	-1.096^a	2.408^b
P值			0.042		0.031			0.062	0.276	0.121

组别	例数	肿瘤边缘不规则[例(%)]	淋巴结转移[例(%)]	TBIL(x±s，μmol/L)	病因[例(%)]				吸烟[例(%)]	饮酒[例(%)]
组别	例数	肿瘤边缘不规则[例(%)]	淋巴结转移[例(%)]	TBIL(x±s，μmol/L)	HBsAg阳性	丙肝抗体	酒精性肝病	其他	吸烟[例(%)]	饮酒[例(%)]
存活组	56	9(16.07)	3(5.36)	80.35±19.43	46(82.14)	3(5.36)	3(5.36)	4(7.14)	10(17.86)	4(7.14)
死亡组	26	8(30.77)	2(7.69)	83.04±15.27	20(76.92)	3(11.54)	2(7.69)	1(3.85)	3(11.54)	1(3.85)
统计量		2.334^b	0.169^b	-0.622^a	-0.425^b				0.531^b	0.337^b
P值		0.127	0.681	0.536	0.671				0.466	0.562
注：^a为t值，^b为χ²值，^c为Z值。

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表 4 复发性肝癌患者总生存率相关因素COX回归分析

因素	B	SE	Wald χ²	P值	HR值	95% CI
术前AFP水平	0.012	0.004	9.768	0.002	1.012	1.005~1.020
最大肿瘤直径	0.173	0.068	6.527	0.011	1.189	1.041~1.358
肿瘤近肝门 < 2 cm	2.138	0.925	5.335	0.021	8.479	1.382~52.010
Child-Pugh A级	0.894	0.874	1.046	0.306	2.444	0.441~13.539
BCLC分级			2.857	0.240
BCLC C级					1.000
BCLC A级	-2.010	1.193	2.839	0.092	0.134	0.013~1.388
BCLC B级	-0.467	1.003	0.217	0.641	0.627	0.088~4.471

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参考文献(20)

[1]	杨绍梅, 张娜. 肝癌治疗药物的研究进展[J]. 中国新药与临床杂志, 2015, 34(2): 93-98. https://www.cnki.com.cn/Article/CJFDTOTAL-XYYL201502003.htm
[2]	HIROKAWA F, HAYASHI M, ASAKUMA M, et al. Risk factors and patterns of early recurrence after curative hepatectomy for hepatocellular carcinoma[J]. Surg Oncol, 2016, 25(1): 24-29. doi: 10.1016/j.suronc.2015.12.002
[3]	DI COSTANZO G G, TORTORA R, D'ADAMO G, et al. Radiofrequency ablation versus laser ablation for the treatment of small hepatocellular carcinoma in cirrhosis: A randomized trial[J]. J Gastroenterol Hepatol, 2015, 30(3): 559-565. doi: 10.1111/jgh.12791
[4]	YOON S M, RYOO B Y, LEE S J, et al. Efficacy and safety of transarterial chemoembolization plus external beam radiotherapy vs sorafenib in hepatocellular carcinoma with macroscopic vascular invasion: a randomized clinical trial[J]. JAMA Oncol, 2018, 4(5): 661-669. doi: 10.1001/jamaoncol.2017.5847
[5]	CHANG L, WANG Y, ZHANG J, et al. The best strategy for HCC patients at each BCLC stage: a network meta-analysis of observational studies[J]. Oncotarget, 2017, 8(12): 20418-20427. doi: 10.18632/oncotarget.14668
[6]	LI W, MAN W, GUO H, et al. Clinical study of transcatheter arterial chemoembolization combined with microwave ablation in the treatment of advanced hepatocellular carcinoma[J]. J Cancer Res Ther, 2016, 12(Supplement): C217-C220. http://europepmc.org/abstract/MED/28230020
[7]	郭欢庆, 闫鹏, 邹常咏, 等. TACE联合微波消融治疗大肝癌的初步研究[J]. 实用放射学杂志, 2015, 31(10): 1692-1694, 1730. doi: 10.3969/j.issn.1002-1671.2015.10.030
[8]	SUN A, CHENG Z, WU P, et al. Clinical outcome of medium-sized hepatocellular carcinoma treated with microwave ablation[J]. World J Gastroenterol, 2015, 21(10): 2997-3004. doi: 10.3748/wjg.v21.i10.2997
[9]	李前进, 刘兴贵. 肝癌晚期患者氩氦刀治疗手术前后外周血T、NK细胞表达差异相关研究[J]. 贵州医药, 2015, 39(8): 706-707. doi: 10.3969/j.ISSN.1000-744X.2015.08.010
[10]	白涛, 叶甲舟, 陈洁, 等. TACE联合RFA治疗复发性肝癌的生存期分析[J]. 肿瘤学杂志, 2018, 24(8): 779-782. https://www.cnki.com.cn/Article/CJFDTOTAL-XHON201808007.htm
[11]	SI Z M, WANG G Z, QIAN S, et al. Combination therapies in the management of large (≥5 cm) hepatocellular carcinoma: microwave ablation immediately followed by transarterial chemoembolization[J]. J Vasc Interv Radiol, 2016, 27(10): 1577-1583. doi: 10.1016/j.jvir.2016.02.014
[12]	SAUZAY C, PETIT A, BOURGEOIS A, et al. Alpha-foetoprotein(AFP): A multi-purpose marker in hepatocellular carcinoma[J]. Clin Chim Acta, 2016, 463(12): 39-44. http://www.sciencedirect.com/science/article/pii/S000989811630403X
[13]	甘雨, 田娜娜, 陈华辉, 等. 原发性肝癌患者AFP浓度与临床特点及预后的相关性[J]. 中华肿瘤防治杂志, 2016, 23(14): 958-962. https://www.cnki.com.cn/Article/CJFDTOTAL-QLZL201614012.htm
[14]	赵鹏, 郑加生, 张洪海, 等. 肝动脉导管化疗栓塞联合CT引导精准微波消融治疗原发性肝癌的疗效及影响因素[J]. 中华肿瘤杂志, 2016, 38(2): 138-145. doi: 10.3760/cma.j.issn.0253-3766.2016.02.012
[15]	李蕊利, 万娟. 原发性肝癌射频消融预后的影响因素分析[J]. 现代肿瘤医学, 2015, 23(20): 2970-2972. https://www.cnki.com.cn/Article/CJFDTOTAL-SXZL201520029.htm
[16]	MEHTA N, HEIMBACH J, HARNOIS D M, et al. Validation of a risk estimation of tumor recurrence after transplant (RETREAT) score for hepatocellular carcinoma recurrence after liver transplant[J]. JAMA Oncol, 2017, 3(4): 493-500. doi: 10.1001/jamaoncol.2016.5116
[17]	BIEDERMAN D M, TITANO J J, BISHAY V L, et al. Radiation segmentectomy versus TACE combined with microwave ablation for unresectable solitary hepatocellular carcinoma up to 3 cm: a propensity score matching study[J]. Radiology, 2017, 283(3): 895-905. doi: 10.1148/radiol.2016160718
[18]	ABDELAZIZ AO, NABEEL M M, ELBAZ T M, et al. Microwave ablation versus transarterial chemoembolization in large hepatocellular carcinoma: prospective analysis[J]. Scand J Gastroenterol, 2015, 50(4): 479-484. doi: 10.3109/00365521.2014.1003397
[19]	FARSAD K, COSTENTIN C E, ZHU A X. Hepatocellular carcinoma with portal venous invasion: radiating new hope?[J]. JAMA Oncol, 2018, 4(5): 669-670. doi: 10.1001/jamaoncol.2018.0007
[20]	YUAN Z H, WANG Y, HU C X, et al. Efficacy of percutaneous thermal ablation combined with transarterial embolization for recurrent hepatocellular carcinoma after hepatectomy and a prognostic nomogram to predict survival[J]. Technol Cancer Res Treat, 2018, 17(8): 1-13. http://www.ncbi.nlm.nih.gov/pubmed/30244651