临床特征与剂量学因素对局部晚期胸段食管鳞状细胞癌患者长期生存影响的分析

摘要/Abstract

摘要：

目的探究临床特征与剂量学因素对局部晚期胸段食管鳞状细胞癌同步放化疗后患者的生存及预后的影响。方法选取2015年8月至2018年10月山东省肿瘤医院、河南省安阳市肿瘤医院、山东省滕州市中心人民医院及中国医科大学附属第一医院收治的158例行同步放化疗的局部晚期胸段食管鳞状细胞癌患者作为研究对象,根据放疗剂量的不同将患者分为标准剂量组(50.0~50.4 Gy,n=59)和高剂量组(>50.4 Gy,n=99)。比较两组患者治疗后的总生存期(OS)以及无进展生存期(PFS)。患者生存率的估算采用Kaplan-Meier法,组间比较采用log-rank检验;Cox比例风险回归模型分析预后不良因素;受试者工作特征(ROC)曲线分析双肺V₃₀对患者预后的预测价值。结果158例局部晚期食管鳞状细胞癌患者同步放化疗治疗后,完全缓解19例,占12.03%;部分缓解103例,占65.19%;病情稳定27例,占17.09%;疾病进展9例,占5.70%。总有效率为77.22%。158例患者的中位OS为41个月(95%CI为25~57个月),1、3年OS率分别为76%、51%;中位PFS为24个月(95%CI为13~35个月),1、3年PFS率分别为60%、39%。其中标准剂量组患者的1、3年OS率分别为74%、56%,高剂量组分别为77%、49%,差异无统计学意义(χ²=0.300,P=0.584);标准剂量组患者的1、3年PFS率分别为62%、37%,高剂量组分别为59%、40%,差异无统计学意义(χ²<0.001,P=0.990)。单因素分析显示,病变长度,N分期,临床分期,同步放化疗近期疗效,计划靶体积(PTV) D_max,大体肿瘤靶体积(GTV) D_mean,左肺、右肺及双肺的V₅、V₁₀、V₂₀、V₃₀、D_mean均是影响患者OS、PFS的预后影响因素(均P<0.05)。多因素分析显示,病变长度(HR=2.226,95%CI为1.244~3.985,P=0.007)、N分期(HR=2.819,95%CI为1.137~6.991,P=0.025)、临床分期(HR=1.897,95%CI为1.079~3.334,P=0.026)、同步放化疗近期疗效(HR=1.805,95%CI为1.250~2.606,P=0.002)、左肺V₁₀(HR=0.811,95%CI为0.668~0.986,P=0.035)、左肺V₃₀(HR=0.617,95%CI为0.408~0.933,P=0.022)、右肺V₂₀(HR=2.067,95%CI为1.010~4.231,P=0.047)、双肺V₁₀(HR=1.299,95%CI为1.016~1.662,P=0.037)及V₃₀(HR=2.368,95%CI为1.142~4.910,P=0.021)均是影响患者OS的独立预后因素;N分期(HR=2.433,95%CI为1.201~4.931,P=0.014)、同步放化疗近期疗效(HR=2.067,95%CI为1.391~3.071,P<0.001)及双肺V₃₀(HR=0.113,95%CI为0.018~0.719,P=0.021)均是影响患者PFS的独立预后因素。预测OS和PFS的ROC曲线显示,双肺V₃₀的最佳临界值均为9.5%。结论与标准剂量组相比,提高放疗剂量未能改善局部晚期胸段食管鳞状细胞癌患者的远期生存。病变长度,N分期,临床分期,同步放化疗近期疗效,左肺的V₁₀、V₃₀,右肺V₂₀及双肺的V₁₀、V₃₀均为局部晚期胸段食管鳞状细胞癌患者OS的独立预后因素,N分期、同步放化疗近期疗效及双肺V₃₀均为患者PFS的独立预后因素。当双肺V₃₀≤9.5%时,患者的OS和PFS均可从治疗中获益。

关键词:食管肿瘤,肿瘤,鳞状细胞,化放疗,预后,剂量学因素

Abstract:

ObjectiveTo explore the effects of clinical characteristics and dosimetric factors on the survival and prognosis of patients with locally advanced thoracic esophageal squamous cell carcinoma after concurrent chemoradiotherapy (CCRT).MethodsA total of 158 patients with locally advanced thoracic esophageal squamous cell carcinoma undergoing CCRT in Shandong Cancer Hospital, Anyang Cancer Hospital of Henan Province, Tengzhou Central People's Hospital of Shandong Province and the First Affiliated Hospital of China Medical University from August 2015 to October 2018 were selected as the research subjects. These patients were divided into standard-dose group (50.0-50.4 Gy,n=59) and high-dose group (>50.4 Gy,n=99) according to the radiotherapy dose. The overall survival (OS) and progression-free survival (PFS) of the two groups after treatment were compared. Kaplan-Meier method was used to calculate survival rate and survival comparison was performed by log-rank test. Cox proportional hazard regression model was used to analyze the adverse prognostic factors. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of lung V₃₀for patient prognosis.ResultsIn 158 patients with locally advanced esophageal squamous cell carcinoma, 19 cases (12.03%) had complete remission after CCRT, 103 cases (65.19%) had partial remission, 27 cases (17.09%) had stable disease, 9 cases (5.70%) had progression disease, and the total effective rate was 77.22%. The median OS of 158 patients was 41 months (95%CI: 25-57 months), and the 1- and 3-year OS rates were 76% and 51%, respectively. The median PFS was 24 months (95%CI: 13-35 months), and the 1- and 3-year PFS rates were 60% and 39%, respectively. The 1- and 3-year OS rates in the standard-dose group were 74% and 56%, and those in the high-dose group were 77% and 49%, with no statistically significant difference (χ²=0.300,P=0.584). The 1- and 3-year PFS rates in the standard-dose group were 62% and 37%, and those in the high-dose group were 59% and 40%, with no statistically significant difference (χ²<0.001,P=0.990). Univariate analysis showed that the length of the lesion, N stage, clinical stage, short-term efficacy of CCRT, planning target volume (PTV) D_max, gross tumor volume (GTV) D_mean, V₅, V₁₀, V₂₀, V₃₀, D_meanof the left, right and bilateral lung were all the prognostic factors for OS and PFS (allP<0.05). Multivariate analysis showed that the length of the lesion (HR=2.226, 95%CI: 1.244-3.985,P=0.007), N stage (HR=2.819, 95%CI: 1.137-6.991,P=0.025), clinical stage (HR=1.897, 95%CI: 1.079-3.334,P=0.026), short-term efficacy of CCRT (HR=1.805, 95%CI: 1.250-2.606, P=0.002), left lung V₁₀(HR=0.811, 95%CI: 0.668-0.986,P=0.035), left lung V₃₀(HR=0.617, 95%CI: 0.408-0.933,P=0.022), right lung V₂₀(HR=2.067, 95%CI: 1.010-4.231,P=0.047), bilateral lung V₁₀(HR=1.299, 95%CI: 1.016-1.662,P=0.037) and bilateral lung V₃₀(HR=2.368, 95%CI: 1.142-4.910,P=0.021) were independent prognostic factors affecting OS. N stage (HR=2.433, 95%CI: 1.201-4.931,P=0.014), short-term efficacy of CCRT (HR=2.067, 95%CI: 1.391-3.071,P<0.001) and bilateral lung V₃₀(HR=0.113, 95%CI: 0.018-0.719,P=0.021) were independent prognostic factors affecting PFS. The ROC curve for predicting OS and PFS showed that the optimal cut-off value of bilateral lung V₃₀was 9.5%.ConclusionCompared with the standard-dose group, increasing the dose of radiotherapy fails to improve the long-term survival of patients with locally advanced thoracic squamous cell carcinoma. Lesion length, N stage, clinical stage, short-term efficacy of CCRT, left lung V₁₀and V₃₀, right lung V₂₀, bilateral lung V₁₀and V₃₀are independent prognostic factors for OS in patients with locally advanced thoracic squamous cell carcinoma. N stage, short-term efficacy of CCRT and bilateral lung V₃₀are independent prognostic factors for PFS. When bilateral lung V₃₀≤9.5%, the patients' OS and PFS will benefit from the treatment.

Key words:Esophageal neoplasms,Neoplasms,squamous cell,Chemoradiotherapy,Prognosis,Dosimetric factors

李晓琴, 张开贤, 李光, 郑安平, 李宝生. 临床特征与剂量学因素对局部晚期胸段食管鳞状细胞癌患者长期生存影响的分析[J]. 国际肿瘤学杂志, 2021, 48(6): 341-349.

Li Xiaoqin, Zhang Kaixian, Li Guang, Zheng Anping, Li Baosheng. Analysis of clinical characteristics and dosimetric factors on long-term survival in locally advanced thoracic esophageal squamous cell carcinoma[J]. Journal of International Oncology, 2021, 48(6): 341-349.

图/表9

图1

图2

表1

影响158例行同步放化疗局部晚期食管鳞状细胞癌患者预后的临床特征单因素分析(%)"

影响因素	例数	1年OS率	3年OS率	χ²值	P值	1年PFS率	3年PFS率	χ²值	P值
性别
男	129	75	49	1.060	0.303	59	40	0.154	0.695
女	29	81	60			68	38
年龄(岁)
≤65	108	75	54	0.162	0.688	59	39	0.549	0.459
>65	50	79	46			64	41
肿瘤位置
上段	76	75	50			59	39
中段	67	73	51	0.565	0.754	59	40	0.596	0.742
下段	15	93	54			73	38
病变长度(cm)
≤5	84	88	66	12.437	<0.001	70	46	7.858	0.005
>5	74	35	35			49	32
T分期
T₂	20	89	65			80	37
T₃	114	75	49	2.435	0.296	56	38	0.820	0.664
T₄	24	70	46			62	49
N分期
N₀	30	93	79	9.577	0.002	86	55	7.034	0.008
N₁	128	72	45			54	36
M分期
M₀	120	81	54	5.667	0.059	64	39	2.526	0.283
M₁	38	61	41			50	39
临床分期
Ⅱ	35	91	71			82	48
Ⅲ	85	77	48	9.287	0.010	56	35	4.959	0.042
Ⅳa	38	61	41			50	39
化疗方案
替吉奥	9	67	33			33	33
FP方案	120	76	58	3.139	0.208	65	41	3.610	0.165
TP方案	29	79	32			46	29
同步放化疗近期疗效
CR	19	95	77			74	50
PR	103	78	51	18.270	<0.001	64	40	52.013	<0.001
SD	27	72	44			56	38
PD	9	14	-			-	-

表1

表2

影响158例行同步放化疗局部晚期食管鳞状细胞癌患者预后的剂量学因素单因素分析"

影响因素	OS				PFS
影响因素	HR值	95%CI	P值		HR值		95%CI		P值
PTV
D_max	1.056	1.010~1.105	0.013	1.053		1.011~1.097		0.013
D_min	0.987	0.969~1.006	0.179	0.992		0.976~1.009		0.359
D_mean	1.036	0.989~1.085	0.139	1.040		0.997~1.085		0.071
GTV
D_max	1.108	0.987~1.049	0.259	1.013		0.985~1.040		0.369
D_min	1.002	0.983~1.021	0.840	1.006		0.989~1.024		0.480
D_mean	1.053	1.003~1.105	0.038	1.055		1.010~1.103		0.017
脊髓
D_max	1.041	0.989~1.095	0.122	1.026		0.982~1.072		0.258
D₂	1.044	0.991~1.100	0.108	1.022		0.977~1.070		0.347
心脏
V₂₅	1.006	0.995~1.106	0.278	1.004		0.995~1.103		0.394
V₃₀	1.008	0.995~1.021	0.208	1.004		0.994~1.107		0.377
V₄₀	1.018	0.999~1.037	0.057	1.011		0.993~1.028		0.227
V₅₀	1.034	0.997~1.072	0.071	1.019		0.984~1.055		0.296
D_mean	1.013	0.993~1.035	0.202	1.008		0.990~1.027		0.396
左肺
V₅	1.019	1.005~1.034	0.007	1.015		1.002~1.028		0.027
V₁₀	1.030	1.011~1.049	0.002	1.027		1.010~1.045		0.002
V₂₀	1.052	1.023~1.081	<0.001	1.040		1.015~1.065		0.002
V₃₀	1.071	1.032~1.111	<0.001	1.055		1.020~1.091		0.002
D_mean	1.124	1.054~1.999	<0.001	1.103		1.040~1.070		0.001
右肺
V₅	1.018	1.004~1.032	0.009	1.016		1.004~1.029		0.012
V₁₀	1.027	1.009~1.045	0.002	1.026		1.009~1.043		0.002
V₂₀	1.046	1.015~1.078	0.004	1.040		1.010~1.070		0.009
V₃₀	1.082	1.031~1.135	0.001	1.064		1.016~1.114		0.008
D_mean	1.121	1.043~1.205	0.002	1.109		1.035~1.188		0.003
双肺
V₅	1.020	1.006~1.035	0.006	1.107		1.004~1.030		0.012
V₁₀	1.033	1.013~1.053	0.001	1.032		1.013~1.051		0.001
V₂₀	1.060	1.026~1.095	<0.001	1.049		1.018~1.030		0.002
V₃₀	1.102	1.050~1.155	<0.001	1.080		1.033~1.129		0.001
D_mean	1.143	1.061~1.232	<0.001	1.123		1.047~1.204		0.001

表2

临床分期	例数	标准剂量组(n=59)		χ²值	P值
Ⅱ	35	92	92	90	59	2.630	0.105
Ⅲ	85	73	46	80	49	0.282	0.595
Ⅳa	38	62	46	61	38	0.109	0.741

表3

临床分期	例数	标准剂量组(n=59)		χ²值	P值
Ⅱ	35	92	62	77	39	1.036	0.309
Ⅲ	85	58	26	55	40	0.225	0.635
Ⅳa	38	46	38	50	32	0.003	0.960

表4

表5

影响158例行同步放化疗局部晚期食管鳞状细胞癌患者OS和PFS的多因素分析"

影响因素	OS				PFS
影响因素	HR值	95%CI	P值		HR值		95%CI		P值
病变长度	2.226	1.244~3.985	0.007	1.518		0.919~2.506		0.103
N分期	2.819	1.137~6.991	0.025	2.433		1.201~4.931		0.014
临床分期	1.897	1.079~3.334	0.026	1.290		0.762~2.185		0.344
同步放化疗近期疗效	1.805	1.250~2.606	0.002	2.067		1.391~3.071		<0.001
PTV D_max	1.036	0.920~1.167	0.556	1.000		0.888~1.125		0.995
GTV D_mean	1.011	0.892~1.146	0.862	1.039		0.921~1.172		0.536
左肺
V₅	0.915	0.676~1.239	0.567	1.000		0.779~1.284		1.000
V₁₀	0.811	0.668~0.986	0.035	0.94		0.791~1.118		0.486
V₂₀	1.805	1.038~3.137	0.060	1.093		0.716~1.669		0.679
V₃₀	0.617	0.408~0.933	0.022	0.791		0.551~1.135		0.204
D_mean	2.410	0.501~11.589	0.272	2.727		0.963~7.721		0.059
右肺
V₅	0.927	0.665~1.292	0.656	1.037		0.785~1.371		0.797
V₁₀	1.010	0.933~1.093	0.813	1.025		0.952~1.104		0.513
V₂₀	2.067	1.010~4.231	0.047	1.141		0.650~2.002		0.647
V₃₀	0.888	0.614~1.283	0.527	0.859		0.634~1.166		0.330
D_mean	0.417	0.066~2.651	0.354	1.382		0.348~5.496		0.646
双肺
V₅	1.323	0.707~2.472	0.380	1.011		0.607~1.683		0.967
V₁₀	1.299	1.016~1.662	0.037	1.143		0.914~1.428		0.241
V₂₀	0.325	0.097~1.091	0.069	0.865		0.339~2.206		0.761
V₃₀	2.368	1.142~4.910	0.021	0.113		0.018~0.719		0.021
D_mean	0.254	0.014~4.574	0.353	1.785		0.961~3.316		0.067

表5

图3

图4

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