局部晚期鼻咽癌诱导化疗后肿瘤退缩率对患者生存的预测价值

摘要/Abstract

摘要：

目的探讨局部晚期鼻咽癌诱导化疗后肿瘤退缩率对生存预后的预测价值。方法选择2009年1月至2012年12月在陆军军医大学大坪医院初治的161例Ⅲ~ⅣA期鼻咽癌患者作为研究对象,分析鼻咽癌患者诱导化疗前后肿瘤体积变化与患者生存时间的关系。采用Kaplan-Meier法绘制生存曲线并行log-rank检验,采用Cox回归分析影响鼻咽癌患者预后的危险性因素。结果鼻咽原发肿瘤诱导化疗后肿瘤退缩率在N_2-3期和N₁期(Z=2.177,P=0.029)及T_1-2期和T_3-4期(Z=-4.501,P<0.001)患者间差异均有统计学意义。在N₁期患者中,诱导化疗后鼻咽原发肿瘤达到(n=18)与未达到客观缓解患者(n=19)的5年总生存(OS)率分别为88.89%、57.45%,颈部淋巴结转移肿瘤达到(n=19)与未达到客观缓解患者(n=18)的5年OS率分别为86.72%、49.10%,差异均有统计学意义(χ²=6.023,P=0.014;χ²=7.441,P=0.006);N_2-3期患者中,诱导化疗后鼻咽原发肿瘤达到(n=81)和未达到客观缓解患者(n=43)的5年OS率分别为77.56%、50.70%,颈部淋巴结转移肿瘤达到(n=85)与未达到客观缓解患者(n=39)的5年OS率分别为75.11%、52.04%,差异均有统计学意义(χ²=8.037,P=0.005;χ²=7.268,P=0.007)。单因素Cox回归分析表明,在N₁期患者中,诱导化疗后鼻咽原发肿瘤退缩率(HR=0.048,95%CI为0.004~0.644,P=0.022)、鼻咽原发肿瘤疗效(HR=0.174,95%CI为0.037~0.830,P=0.028)和颈部淋巴结转移肿瘤疗效(HR=0.154,95%CI为0.033~0.725,P=0.017)均与OS相关;在N_2-3期患者中,诱导化疗后鼻咽原发肿瘤退缩率(HR=0.178,95%CI为0.056~0.564,P=0.003)、颈部淋巴结转移肿瘤退缩率(HR=0.081,95%CI为0.020~0.324,P<0.001)、鼻咽原发肿瘤疗效(HR=0.422,95%CI为0.228~0.781,P=0.006)和颈部淋巴结转移肿瘤疗效(HR=0.439,95%CI为0.238~0.813,P=0.009)均与OS相关;在包含N分期和肿瘤退缩率以及N分期和疗效的多因素Cox回归中,交互项均未达到统计学意义(均P>0.05)。在T_1-2期患者中,诱导化疗后鼻咽原发肿瘤达到(n=45)与未达到客观缓解患者(n=13)的5年OS率分别为77.55%、84.62%,颈部淋巴结转移肿瘤达到(n=43)与未达到客观缓解患者(n=15)的5年OS率分别为78.89%、80.00%,差异均无统计学意义(χ²=0.239,P=0.625;χ²=0.005,P=0.943);在T_3-4期患者中,诱导化疗后鼻咽原发肿瘤达到(n=54)与未达到客观缓解患者(n=49)的5年OS率分别为78.90%、45.00%,颈部淋巴结转移肿瘤达到(n=61)与未达到客观缓解患者(n=42)的5年OS率分别为75.10%、42.89%,差异均有统计学意义(χ²=13.615,P<0.001;χ²=12.752,P<0.001)。单因素Cox回归分析表明,在T_1-2期患者中,诱导化疗后肿瘤退缩率、鼻咽原发肿瘤及颈部淋巴结转移肿瘤疗效均与OS无关(均P>0.05);在T_3-4期患者中,诱导化疗后鼻咽原发肿瘤退缩率(HR=0.121,95%CI为0.033~0.444,P=0.001)、颈部淋巴结转移肿瘤退缩率(HR=0.126,95%CI为0.036~0.442,P=0.001)、鼻咽原发肿瘤疗效(HR=0.297,95%CI为0.150~0.588,P<0.001)和颈部淋巴结转移肿瘤疗效(HR=0.329,95%CI为0.173~0.625,P=0.001)均与OS相关;多因素Cox回归分析发现,鼻咽原发肿瘤疗效与T分期交互项接近统计学意义(P=0.062)。结论Ⅲ~ⅣA期鼻咽癌患者中,T_3-4期患者诱导化疗后鼻咽部原发病灶缓解情况对预测生存预后具有重要价值。

关键词:鼻咽肿瘤,放射疗法,药物疗法,治疗结果,预后

Abstract:

ObjectiveTo investigate the predictive value of tumor regression rate after induction chemotherapy for survival of patients with locally advanced nasopharyngeal carcinoma.MethodsA total of 161 patients with stage Ⅲ-ⅣA nasopharyngeal carcinoma newly diagnosed at the Daping Hospital of Army Medical University from January 2009 to December 2012 were selected as the research subjects. The relationships between tumor size changes before and after induction chemotherapy and survival time were analyzed. Kaplan-Meier method was used to draw the survival curve accompanied with log-rank test. Cox regression analysis was used to analyze the risk factors affecting the prognosis of patients with nasopharyngeal carcinoma.ResultsThere were statistically significant differences in the tumor regression rate of primary lesions between N₁and N_2-3(Z=2.177,P=0.029), T_1-2and T_3-4(Z=-4.501,P<0.001)patients after induction chemotherapy. In N₁stage patients, the 5-year overall survival (OS) rates of patients with primary lesions achieving objective response (n=18) and those without objective response (n=19) after induction chemotherapy were 88.89% and 57.45%, and patients with cervical lymph node metastatic lesions achieving objective response (n=19) and those without objective response (n=18) were 86.72% and 49.10% respectively, with statistically significant differences (χ²=6.023,P=0.014;χ²=7.441,P=0.006). In N_2-3stage patients, the 5-year OS rates of patients with primary lesions achieving objective response (n=81) and those without objective response (n=43) after induction chemotherapy were 77.56% and 50.70%, and patients with cervical lymph node metastatic lesions achieving objective response (n=85) and those without objective response (n=39) were 75.11% and 52.04% respectively, with significant differences (χ²=8.037,P=0.005;χ²=7.268,P=0.007). Univariate Cox regression analysis showed that in patients with stage N₁, the tumor regression rate of primary lesions (HR=0.048, 95%CI: 0.004-0.644,P=0.022), the efficacy of primary lesions (HR=0.174, 95%CI: 0.037-0.830,P=0.028), the efficacy of cervical lymph node metastatic lesions (HR=0.154, 95%CI: 0.033-0.725,P=0.017) after induction chemotherapy were significantly associated with OS; in N_2-3stage patients, the tumor regression rate of primary lesions (HR=0.178, 95%CI: 0.056-0.564,P=0.003), the tumor regression rate of cervical lymph node metastatic lesions (HR=0.081, 95%CI: 0.020-0.324,P<0.001), the efficacy of primary lesions (HR=0.422, 95%CI: 0.228-0.781,P=0.006), the efficacy of cervical lymph node metastatic lesions (HR=0.439, 95%CI: 0.238-0.813,P=0.009) after induction chemotherapy were significantly associated with OS. In multivariate Cox regression including N stage and tumor regression rate, N stage and efficacy, the interaction items were not statistically significant (allP>0.05). In T_1-2stage patients, the 5-year OS rates of patients with primary lesions achieving objective response (n=45) and those without objective response (n=13) after induction chemotherapy were 77.55% and 84.62%, and patients with cervical lymph node metastatic lesions achieving objective response (n=43) and those without objective response (n=15) were 78.89% and 80.00% respectively, with no significant differences (χ²=0.239,P=0.625;χ²=0.005,P=0.943); in T_3-4stage patients, the 5-year OS rates of patients with primary lesions achieving objective response (n=54) and those without objective response (n=49) after induction chemotherapy were 78.90% and 45.00%, and patients with cervical lymph node metastatic lesions achieving objective response (n=61) and those without objective response (n=42) were 75.10% and 42.89% respectively, with significant differences (χ²=13.615,P<0.001;χ²=12.752,P<0.001). Univariate Cox regression analysis showed that in patients with stage T_1-2, the tumor regression rate, the efficacy of primary lesions and cervical lymph node metastatic lesions after induction chemotherapy were not related to OS (allP>0.05); in T_3-4stage patients, the tumor regression rate of primary lesions (HR=0.121, 95%CI: 0.033-0.444,P=0.001), the tumor regression rate of cervical lymph node metastatic lesions (HR=0.126, 95%CI: 0.036-0.442,P=0.001), the efficacy of primary lesions (HR=0.297, 95%CI: 0.150-0.588,P<0.001), the efficacy of cervical lymph node metastatic lesions (HR=0.329, 95%CI: 0.173-0.625,P=0.001) after induction chemotherapy were significantly associated with OS. Multivariate Cox regression analysis showed that the interaction test of T stage and the efficacy of primary lesion trended to be statistically significant (P=0.062).ConclusionIn patients with stage Ⅲ-ⅣA nasopharyngeal carcinoma, the responsiveness to induction chemotherapy in stage T_3-4patients has important value in predicting survival prognosis.

Key words:Nasopharyngea neoplasms,Radiotherapy,Drug therapy,Treatment outcome,Prognosis

宋扬, 王斌, 肖何, 陈川, 王阁, 耿明英. 局部晚期鼻咽癌诱导化疗后肿瘤退缩率对患者生存的预测价值[J]. 国际肿瘤学杂志, 2021, 48(3): 156-163.

Song Yang, Wang Bin, Xiao He, Chen Chuan, Wang Ge, Geng Mingying. Predictive value of tumor regression rate after induction chemotherapy for survival of patients with locally advanced nasopharyngeal carcinoma[J]. Journal of International Oncology, 2021, 48(3): 156-163.

图/表7

表1

161例不同N分期局部晚期鼻咽癌患者基线特征比较[例(%)/M(P25,P75)]"

临床病理特征	N₁期 (n=37)	N_2-3期 (n=124)	χ²/Z值	P值
性别
女	10(27.0)	38(30.6)	0.178	0.673
男	27(73.0)	86(69.4)
T分期
T₁	0(0)	11(8.9)
T₂	0(0)	47(37.9)	33.201	<0.001
T₃	21(56.8)	39(31.5)
T₄	16(43.2)	27(21.8)
临床分期
Ⅲ	21(56.8)	85(68.5)	1.762	0.184
ⅣA	16(43.2)	39(31.5)
鼻咽原发肿瘤诱导化疗后疗效评价
CR	3(8.1)	20(16.1)
PR	15(40.5)	61(49.2)	3.793	0.150
SD	19(51.4)	43(34.7)
颈部淋巴结诱导化疗后疗效评价
CR	5(13.5)	5(4.0)
PR	14(37.8)	80(64.5)	10.442	0.009
SD	18(48.6)	38(30.6)
PD	0(0)	1(0.8)
年龄(岁)	47(42,56)	47(41,56)	-0.141	0.888
鼻咽原发肿瘤体积(cm³)	3.3(2.3,3.8)	2.8(1.8,3.6)	-1.679	0.093
颈部淋巴结转移肿瘤体积(cm³)	2.5(1.8,3.5)	4.8(3.0,6.8)	5.483	<0.001
鼻咽原发肿瘤诱导化疗后肿瘤退缩率(%)	29.6(8.5,47.8)	44.0(21.1,56.3)	2.177	0.029
颈部淋巴结诱导化疗后肿瘤退缩率(%)	30.4(0.0,51.4)	42.6(16.7,52.0)	1.722	0.085

表1

表2

161例不同T分期局部晚期鼻咽癌患者基线特征比较[例(%)/M(P25,P75)]"

临床病理特征
性别
女	14(24.1)			34(33.0)			1.396			0.237
男	44(75.9)			69(67.0)
N分期
N₁	0(0)			37(35.9)
N₂	50(86.2)			58(56.3)			27.135			<0.001
N₃	8(13.8)			8(7.8)
临床病理特征			T_1-2期 (n=58)			T_3-4期 (n=103)			χ²/Z值		P值
临床分期
Ⅲ		50(86.2)			56(54.4)			16.723				<0.001
ⅣA		8(13.8)			47(45.6)
鼻咽原发肿瘤诱导化疗后疗效评价
CR		17(29.3)			6(5.8)
PR		28(48.3)			48(46.6)			20.447				<0.001
SD		13(22.4)			49(47.6)
颈部淋巴结诱导化疗后疗效评价
CR		3(5.2)			7(6.8)
PR		40(69.0)			54(52.4)			4.437				0.187
SD		15(25.9)			41(39.8)
PD		0(0)			1(1.0)
年龄(岁)		48(41,55)			47(41,57)			0.326				0.744
鼻咽原发肿瘤体积(cm³)		2.0(1.5,2.9)			3.2(2.3,3.8)			4.315				<0.001
颈部淋巴结转移肿瘤体积(cm³)		5.2(4.5,7.6)			3.2(2.4,5.0)			-5.524				<0.001
鼻咽原发肿瘤诱导化疗后肿瘤退缩率(%)		50.0(30.0,100.0)			35.5(10.7,48.8)			-4.501				<0.001
颈部淋巴结诱导化疗后肿瘤退缩率(%)		40.4(29.2,53.7)			37.5(9.1,51.4)			-1.565				0.118

表2

表3

影响161例局部晚期鼻咽癌患者OS的单因素和多因素Cox分析"

参数	单因素			多因素
参数	HR值	95%CI	P值	HR值	95%CI	P值
性别(男/女)	0.988	0.542~1.802	0.970	1.043	0.558~1.949	0.895
年龄(岁)	0.994	0.968~1.020	0.646	0.987	0.961~1.015	0.367
T分期(T_3-4/T_1-2)	2.114	1.108~4.033	0.023	3.339	1.528~7.299	0.003
N分期(N_2-3/N₁)	1.204	0.618~2.344	0.585	1.344	0.634~2.852	0.441
鼻咽原发肿瘤体积(cm³)	1.158	0.921~1.452	0.203	1.235	0.948~1.609	0.118
颈部转移淋巴结体积(cm³)	1.127	1.036~1.227	0.005	1.221	1.094~1.363	<0.001
鼻咽原发肿瘤疗效(CR+PR/SD+PD)	0.384	0.221~0.668	0.001	0.675	0.358~1.276	0.226
颈部淋巴结转移肿瘤疗效(CR+PR/SD+PD)	0.385	0.223~0.664	0.001	0.467	0.254~0.858	0.014

表3

图1

肿瘤退缩情况	N₁期(n=37)		N_2-3期(n=124)
鼻咽原发肿瘤退缩率	0.048	0.004~0.644	0.022	0.178	0.056~0.564	0.003	0.386
颈部淋巴结转移肿瘤退缩率	0.087	0.007~1.070	0.056	0.081	0.020~0.324	<0.001	0.923
鼻咽原发肿瘤疗效(CR+PR/SD+PD)	0.174	0.037~0.830	0.028	0.422	0.228~0.781	0.006	0.353
颈部淋巴结转移肿瘤疗效(CR+PR/SD+PD)	0.154	0.033~0.725	0.017	0.439	0.238~0.813	0.009	0.234

表4

图2

肿瘤退缩情况	T_1-2期(n=58)		T_3-4期(n=103)
鼻咽原发肿瘤退缩率	0.595	0.093~3.802	0.584	0.121	0.033~0.444	0.001	0.161
颈部淋巴结转移肿瘤退缩率	0.111	0.007~1.696	0.114	0.126	0.036~0.442	0.001	0.895
鼻咽原发肿瘤疗效(CR+PR/SD+PD)	1.458	0.319~6.655	0.627	0.297	0.150~0.588	<0.001	0.062
颈部淋巴结转移肿瘤疗效(CR+PR/SD+PD)	0.953	0.258~3.523	0.943	0.329	0.173~0.625	0.001	0.161

表5

参考文献13

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