微波消融联合全身化疗治疗复发性肝内胆管癌的有效性与安全性分析

魏春; 刘宇; 李波; 蒋鸥

doi:10.3969/j.issn.1001-5256.2023.07.015

微波消融联合全身化疗治疗复发性肝内胆管癌的有效性与安全性分析

DOI: 10.3969/j.issn.1001-5256.2023.07.015

魏春^1a,
刘宇²,
李波^1b,
蒋鸥^{1a, 2, , ,}

1a.
西南医科大学附属医院肿瘤科，四川泸州 646000
1b.
西南医科大学附属医院肝胆外科，四川泸州 646000
2.
内江市第二人民医院肿瘤四科，四川内江 641000

基金项目:

国家科技重大专项 (2018zx09303-014);

四川省卫健委课题 (18PJ194)

伦理学声明：本研究方案于2022年4月11日经由内江市第二人民医院伦理委员会审批，批号：2022-0403。

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：魏春、刘宇负责起草及撰写文章；魏春负责数据收集、统计与随访；蒋鸥负责指导思路；李波、蒋鸥负责修改文章并最终定稿。

详细信息

通信作者:
蒋鸥，jiangou866@163.com (ORCID: 0000-0002-6615-8068)

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出版历程
- 收稿日期: 2022-11-03
- 录用日期: 2022-12-18
- 出版日期: 2023-07-20

Efficacy and safety of microwave ablation combined with systemic chemotherapy in treatment of recurrent intrahepatic cholangiocarcinoma

Chun WEI^1a,
Yu LIU²,
Bo LI^1b,
Ou JIANG^{1a, 2
, ,
,}

1a.
Department of Oncology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
1b.
Department of Hepatobiliary Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China
2.
Fourth Department of Oncology, The Second People's Hospital of Neijiang, Neijiang, Sichuan 641000, China

Research funding:

Major National Science and Technology Projects (2018zx09303-014);

Sichuan Provincial Health Commission (18PJ194)

More Information

Corresponding author: JIANG Ou, jiangou866@163.com (ORCID: 0000-0002-6615-8068)

摘要

摘要: 目的探讨微波消融(MWA)联合化疗与单独MWA治疗复发性肝内胆管癌(RICC)的有效性和安全性。方法采用回顾性队列研究方法。选取2014年1月—2021年3月内江市第二人民医院及西南医科大学附属医院接受MWA+ 化疗和单独MWA的RICC患者，收集入组患者的临床病理资料。计量资料两组间比较采用成组t检验，计数资料两组间比较采用χ²检验和Fisher精确检验。釆用Kaplan-Meier法计算无进展生存期(PFS)和总生存期(OS)。使用Log-rank检验方法比较生存差异。应用单因素和多因素Cox比例风险回归模型分析生存预后的危险因素。结果共筛选到106例RICC患者，其中MWA+化疗组55例，MWA组51例。至随访截止，MWA+化疗组的中位PFS为15.0个月(95%CI：14.5~15.5)，MWA组中位PFS为13.4个月(95%CI：11.6~15.2)，两组差异有统计学意义(χ²=9.624，P=0.002)。MWA+化疗组的中位OS为21.0个月(95%CI：20.0~21.8)，MWA组中位OS为18.0个月(95%CI：16.3~19.7)，两组差异有统计学意义(χ²=12.784，P＜0.001)。Cox回归分析显示，肿瘤直径(HR=0.425, 95%CI：0.208~0.868，P=0.019;HR=0.299, 95%CI：0.121~0.739，P=0.009)、复发时间(HR=7.064, 95%CI：3.612~13.618，P＜0.001;HR=2.341, 95%CI：1.072~5.113，P=0.033)及联合化疗(HR=0.138, 95%CI：0.069~0.276，P＜0.001;HR=0.175, 95%CI：0.081~0.380，P＜0.001)是RICC患者PFS和OS的独立影响因素。两组常见不良反应中，除血液学毒性发生率(χ²=12.524，P＜0.001)外，其余不良反应发生率差异均无统计学意义(P值均＞0.05)。结论与单独MWA相比，MWA+化疗可以改善RICC的预后，延长其PFS和OS，且副反应安全可控。肿瘤直径＞5 cm、复发时间＜1年、未联合全身化疗的患者预后不良。
- 胆管上皮癌 /
- 消融技术 /
- 药物疗法
Abstract: Objective To investigate the efficacy and safety of microwave ablation (MWA) combined with chemotherapy versus MWA alone in the treatment of recurrent intrahepatic cholangiocarcinoma (RICC). Methods A retrospective cohort study was conducted among the patients with RICC who received MWA+chemotherapy or MWA in The Second People's Hospital of Neijiang and The Affiliated Hospital of Southwest Medical University from January 2014 to March 2021, and their clinicopathological data were collected. The independent samples t-test was used for comparison of continuous data, and the chi-square test and the Fisher's exact test were used for comparison of categorical data. The Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS), and the Log-rank test was used for comparison of survival differences. Univariate and multivariate Cox proportional-hazards regression model analyses were used to investigate the risk factors for survival and prognosis. Results A total of 106 patients with RIC were enrolled, among whom there were 55 patients in the MWA+chemotherapy group and 51 in the MWA group. By the end of follow-up, the MWA+chemotherapy group had a median PFS of 15.0 months (95% confidence interval [CI]: 14.5-15.5), and the MWA group had a median PFS of 13.4 months (95%CI: 11.6-15.2), with a significant difference between the two groups (χ²=9.624, P=0.002). The MWA+chemotherapy group had a median OS of 21.0 months (95%CI: 20.0-21.8), and the MWA group had a median OS of 18.0 months (95%CI: 16.3-19.7), with a significant difference between the two groups (χ²=12.784, P < 0.001). The Cox regression analysis showed that tumor diameter (PFS: hazard ratio [HR]=0.425, 95%CI: 0.208-0.868, P=0.019; OS: HR=0.299, 95%CI: 0.121-0.739, P=0.009), time to recurrence (PFS: HR=7.064, 95%CI: 3.612-13.618, P < 0.001; OS: HR=2.341, 95%CI: 1.072-5.113, P=0.033), and combined chemotherapy (PFS: HR=0.138, 95%CI: 0.069-0.276, P < 0.001; OS: HR=0.175, 95%CI: 0.081-0.380, P < 0.001) were independent influencing factors for PFS and OS in patients with RICC. As for the common adverse reactions, there were no significant differences in the incidence rates of all adverse reactions except hematological toxicity (χ²=12.524, P < 0.001). Conclusion Compared with MWA alone, MWA combined with chemotherapy can improve the prognosis of RICC and prolong PFS and OS, with safe and controllable side effects. Patients with tumor diameter > 5 cm, time to recurrence < 1 year, and absence of systemic chemotherapy tend to have a poor prognosis.
- Cholangiocarcinoma /
- Ablation Techniques /
- Drug Therapy

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图 1 两组PFS生存曲线

Figure 1. PFS survival curve between the two groups

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图 2 两组OS生存曲线

Figure 2. OS survival curve between the two groups

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表 1 两组基线资料比较

Table 1. Comparison of baseline data between the two groups

项目	MWA+化疗(n=55)	MWA(n=51)	统计值	P值
年龄(岁)	55.008±8.829	55.099±9.070	t=0.211	0.958
男性[例(%)]	39(70.9)	37(72.5)	χ²=0.035	0.851
HBV感染	33(60.0)	27(52.9)	χ²=0.537	0.464
肝硬化[例(%)]	36(65.5)	31(60.8)	χ²=0.248	0.618
TBil(μmol/L)	41.025±13.796	37.208±12.988	t=1.465	0.146
AST(U/L)	65.891±23.122	73.093±24.721	t=-1.551	0.125
ALT(U/L)	69.755±24.965	79.076±35.183	t=-1.562	0.122
Alb(g/L)	38.684±4.069	38.882±3.806	t=-0.265	0.797
PT(s)	14.082±1.326	14.172±1.667	t=-0.310	0.757
INR	1.344±0.197	1.373±0.178	t=-0.806	0.421
CA19-9[例(%)]			χ²=0.621	0.431
≤37 U/mL	36(65.5)	37(72.5)
＞37 U/mL	19(34.5)	14(27.5)
术后复发TNM分期[例(%)]			χ²=0.865	0.649
Ⅰ期	31(56.4)	26(51.0)
Ⅱ期	17(30.9)	20(39.2)
Ⅲ期	7(12.7)	5(9.8)
肿瘤直径[例(%)]			χ²=0.907	0.119
≤5 cm	35(63.6)	26(51.0)
＞5 cm	20(36.4)	25(49.0)
肿瘤个数[例(%)]			χ²=0.794	0.268
1个	41(74.5)	34(66.7)
2~3个	14(25.5)	17(33.3)
首次切除时分化程度[例(%)]			χ²=0.095	0.758
中高度	34(61.8)	33(64.7)
低度	21(38.2)	18(35.3)
Child-Pugh分级[例(%)]			χ²=0.484	0.486
A级	37(67.3)	31(60.8)
B级	18(32.7)	20(39.2)
距初次切除后的复发时间[例(%)]			χ²=2.358	0.125
≤1年	33(60.0)	23(45.1)
＞1年	22(40.0)	28(54.9)
联合TACE[例(%)]			χ²=0.028	0.867
是	38(69.1)	36(70.6)
否	17(30.9)	15(29.4)

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表 2 RICC患者PFS的单因素分析

Table 2. Univariate analysis of PFS in patients with RICC

项目	HR	P值
性别(男/女)	0.708(0.408~1.228)	0.219
年龄(＞60/≤60岁)	1.243(0.729~2.120)	0.423
HBV(+)(是/否)	0.859(0.517~1.426)	0.557
TBil(＞34.2 μmol/L/≤34.2 μmol/L)	2.498(1.497~4.169)	0.001
AST(＞40 U/L/≤40 U/L)	0.754(0.343~1.657)	0.482
ALT(＞40 U/L/≤40 U/L)	1.692(0.760~3.768)	0.198
Alb(＞35 g/L/≤35 g/L)	1.930(1.061~3.512)	0.031
CA19-9(＞37 ng/mL/≤37 ng/mL)	0.326(0.193~0.550)	＜0.001
TNM分期(≥Ⅱ期/Ⅰ期)	1.012(0.727~1.409)	0.943
肿瘤直径(＞5 cm/≤5 cm)	0.353(0.212~0.588)	＜0.001
肿瘤个数(1个/2~3个)	0.778(0.453~1.335)	0.361
分化程度(中高/低)	0.472(0.287~0.775)	0.003
Child-Pugh分级(A/B)	1.165(0.690~1.969)	0.568
复发时间(＞1年/≤1年)	4.286(2.505~7.331)	＜0.001
联合化疗(是/否)	0.437(0.255~0.747)	0.002
联合TACE(是/否)	0.756(0.446~1.281)	0.298

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表 3 RICC患者OS的单因素分析

Table 3. Univariate analysis of OS in patients with RICC

项目	HR	P值
性别(男/女)	0.625(0.329~1.187)	0.151
年龄(＞60岁/≤60岁)	0.753(0.578~2.134)	0.753
HBV(+)(是/否)	0.754(0.413~1.376)	0.357
TBil(＞34.2 μmol/L/≤34.2 μmol/L)	1.570(0.855~2.883)	0.146
AST(＞40 U/L/≤40 U/L)	0.912(0.357~2.332)	0.848
ALT(＞40 U/L/≤40 U/L)	2.010(0.778~5.196)	0.150
Alb(＞35.0 g/L/≤35.0 g/L)	1.429(0.658~3.106)	0.367
CA19-9＞40 ng/mL(是/否)	0.412(0.224~0.756)	0.004
TNM分期(≥Ⅱ期/Ⅰ期)	1.188(0.652~2.166)	0.574
肿瘤直径(＞5 cm/≤5 cm)	0.244(0.127~0.470)	＜0.001
肿瘤个数(1个/2~3个)	0.835(0.427~1.631)	0.598
分化程度(中高/低)	0.502(0.274~0.922)	0.026
Child-Pugh分级(A/B)	0.970(0.512~1.839)	0.927
复发时间(＞1年/≤1年)	2.606(1.382~4.912)	0.003
联合化疗(是/否)	0.339(0.177~0.651)	0.001
联合TACE(是/否)	0.629(0.335~1.179)	0.148

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表 4 两组不良反应比较

Table 4. Comparison of complications between the two groups

项目	MWA+化疗(n=55)		MWA(n=51)		χ²值	P值
项目	所有级别	3~4级	所有级别	3~4级	χ²值	P值
血液学毒性[例(%)]	18(32.7)	2(3.6)	2(3.9)	0(0.0)	12.524	＜0.001
乏力[例(%)]	22(40.0)	3(5.5)	16(31.4)	1(2.0)	0.856	0.355
胃肠道反应[例(%)]	21(38.2)	2(3.6)	11(21.6)	1(2.0)	3.465	0.063
疼痛[例(%)]	18(32.7)	0(0.0)	15(29.4)	2(3.9)	0.136	0.713
肝功能异常[例(%)]	16(29.1)	1(1.8)	10(19.6)	0(0.0)	1.286	0.257
发热[例(%)]	8(14.5)	0(0.0)	4(7.8)	0(0.0)		0.277
出血[例(%)]	1(1.8)	0(0.0)	2(3.9)	0(0.0)		0.607
腹水/胸水[例(%)]	2(3.6)	0(0.0)	4(7.8)	0(0.0)		0.425
血栓[例(%)]	1(1.8)	0(0.0)	0(0.0)	0(0.0)		＞0.05

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