索拉非尼治疗后完全缓解肝癌患者"等待观察"策略安全性分析

doi:10.3877/cma.j.issn.2095-3232.2021.04.014

目的

探讨索拉非尼治疗后完全缓解的肝细胞癌（肝癌）患者采用"等待观察"策略的安全性和可行性。

方法

报道1例肝癌患者接受介入联合索拉非尼治疗达到完全病理缓解。患者已签署知情同意书，符合医学伦理学规定。检索2007年1月至2020年4月PubMed、Embase、Ovid、万方、中国知网、维普网等数据库收录的中英文临床研究文献。英文检索词："hepatocellular carcinoma"、"sorafenib"、"complete response"、"complete pathological response"。中文检索词："肝癌"、"索拉非尼"、"完全缓解"、"完全病理缓解"。统计以索拉非尼为基础治疗后完全缓解患者术后1、3、5年总体生存率和无进展生存率。生存分析采用Kaplan-Meier法和Log-rank检验。

结果

共纳入37篇文献，总计肝癌患者45例，其中男39例，女6例。患者术后1、3、5年总体生存率分别为100%、94.3%、94.3%，无进展生存率分别为100%、89.3%、89.3%。患者性别、年龄、AFP水平、BCLC分期、门静脉癌栓、肝外转移、病毒性肝炎情况、是否全量使用索拉非尼、治疗方案、是否行肝肿瘤切除、缓解情况等因素均不影响患者生存时间（χ²=0.260，1.411，0.219，0.852，0.087，1.838，0.916，1.065，0.539，0.027，0.590；P>0.05）及疾病复发（χ²=0.409，1.899，1.455，3.300，0.853，0.557，1.220，0.006，2.790，0.894，0.384；P>0.05 ）。

结论

以索拉非尼为基础治疗获完全缓解的肝癌患者生存预后明显改善，缓解后采用"等待观察"可能是一种安全有效的策略，不推荐进行肝癌切除或介入治疗。

关键词: 肝肿瘤, 索拉非尼, 完全缓解, 安全性

Objective

To evaluate the safety and feasibility of wait-and-see strategy for primary liver cancer (PLC) patients with complete response after sorafenib treatment.

Methods

1 case of PLC who achieved pathological complete response after interventional therapy combined with sorafenib therapy was reported. The informed consent of this patient was obtained and the local ethical committee approval was received. Relevant clinical studies were searched from PubMed, Embase, Ovid, Wanfang, CNKI and Chongqing VIP databases from January 2007 to April 2020 using the keywords hepatocellular carcinoma, sorafenib, complete response, complete pathological response in both Chinese and English. The 1-, 3- and 5-year overall survival and progression-free survival of PLC patients with complete response after sorafenib-based treatments were calculated. Survival analysis was conducted by Kaplan-Meier method and Log-rank test.

Results

37 articles of 45 PLC patients, 39 male and 6 female, were included. The 1-, 3-, and 5-year overall survival rates were 100%, 94.3%, and 94.3%, and the progression-free survival rates were 100%, 89.3%, and 89.3%, respectively. Gender, age, AFP level, BCLC staging, portal vein tumor thrombus, extrahepatic metastasis, viral hepatitis, use of full-dose sorafenib, therapeutic regimen, resection of liver tumor and condition of remission were not significantly associated with the survival of patients (χ²=0.260, 1.411, 0.219, 0.852, 0.087, 1.838, 0.916, 1.065, 0.539, 0.027, 0.590; P>0.05) and disease recurrence (χ²=0.409, 1.899, 1.455, 3.300, 0.853, 0.557, 1.220, 0.006, 2.790, 0.894, 0.384; P>0.05).

Conclusions

PLC patients who achieve complete response after sorafenib-based treatments can obtain favorable clinical prognosis. Application of wait-and-see strategy is a safe option. Liver tumor resection or interventional therapy is not recommended.

Key words: Liver neoplasms, Sorafenib, Complete remission, Safety

图1 一例以索拉非尼为基础治疗后完全缓解肝癌患者MRI及病理检查

表1 以索拉非尼为基础治疗后完全缓解肝癌患者基本信息

参数		例数	5年总体生存率（%）	χ²值	P值	5年无进展生存率（%）	χ²值	P值
性别				0.260	0.610		0.409	0.522
	男	39	93.6			87.4
	女	6	100			100
年龄（岁）				1.411	0.235		1.899	0.168
	>60	22	100			100
	≤60	23	90.4			82.2
AFP（μg/L）				0.219	0.64		1.455	0.228
	>400	29	96.0			82.5
	≤400	16	90.9			100
BCLC分期				0.852	0.653		3.300	0.192
	A期	11	100			75
	B期	3	100			100
	C期	31	92.0			92.9
门静脉癌栓				0.087	0.768		0.853	0.356
	有	24	95.0			90.9
	无	21	93.8			84.6
肝外转移				1.838	0.175		0.557	0.445
	有	10	85.7			100
	无	35	96.4			88.6
病毒性肝炎				0.916	0.339		1.220	0.269
	有	32	91.8			84.6
	无	13	100			100
全量服用索拉非尼				1.065	0.302		0.006	0.941
	是	16	100			91.7
	否	29	91.3			88.4
治疗方案				0.539	0.463		2.790	0.095
	索拉非尼+介入	13	90.9			77.8
	单药索拉非尼	19	95.8			99.3
肝肿瘤切除				0.027	0.870		0.894	0.334
	是	18	95.2			86.2
	否	27	92.9			92.3
缓解情况				0.590	0.442		0.384	0.535
	完全缓解	35	92.7			90.0
	完全病理缓解	10	100			87.5

表1 以索拉非尼为基础治疗后完全缓解肝癌患者基本信息

参数		例数	5年总体生存率（%）	χ²值	P值	5年无进展生存率（%）	χ²值	P值
性别				0.260	0.610		0.409	0.522
	男	39	93.6			87.4
	女	6	100			100
年龄（岁）				1.411	0.235		1.899	0.168
	>60	22	100			100
	≤60	23	90.4			82.2
AFP（μg/L）				0.219	0.64		1.455	0.228
	>400	29	96.0			82.5
	≤400	16	90.9			100
BCLC分期				0.852	0.653		3.300	0.192
	A期	11	100			75
	B期	3	100			100
	C期	31	92.0			92.9
门静脉癌栓				0.087	0.768		0.853	0.356
	有	24	95.0			90.9
	无	21	93.8			84.6
肝外转移				1.838	0.175		0.557	0.445
	有	10	85.7			100
	无	35	96.4			88.6
病毒性肝炎				0.916	0.339		1.220	0.269
	有	32	91.8			84.6
	无	13	100			100
全量服用索拉非尼				1.065	0.302		0.006	0.941
	是	16	100			91.7
	否	29	91.3			88.4
治疗方案				0.539	0.463		2.790	0.095
	索拉非尼+介入	13	90.9			77.8
	单药索拉非尼	19	95.8			99.3
肝肿瘤切除				0.027	0.870		0.894	0.334
	是	18	95.2			86.2
	否	27	92.9			92.3
缓解情况				0.590	0.442		0.384	0.535
	完全缓解	35	92.7			90.0
	完全病理缓解	10	100			87.5

图2 以索拉非尼为基础治疗后完全缓解肝癌患者Kaplan-Meier生存曲线

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Safety of wait-and-see strategy for primary liver cancer patients with complete response after sorafenib treatment

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Safety of wait-and-see strategy for primary liver cancer patients with complete response after sorafenib treatment