手术联合放化疗治疗晚期下咽癌的生存及安全性评价

摘要/Abstract

摘要：

目的比较晚期下咽鳞状细胞癌患者接受手术联合放化疗与放化疗治疗的生存情况及不良反应,并分析患者预后影响因素。方法回顾性分析2013年8月至2018年12月就诊于蚌埠医学院第一附属医院肿瘤放疗科的78例晚期下咽鳞状细胞癌患者的临床病理资料,根据治疗方式将患者分为手术联合放化疗组(n=27)和放化疗组(n=51)。中位随访时间为46(20~84)个月,主要观察指标为总生存期(OS)、无进展生存期(PFS)和局部控制率(LCR),采用Cox回归模型分析患者预后影响因素。结果截至2020年7月31日,78例晚期下咽鳞状细胞癌患者死亡51例,其中局部复发6例、远处转移11例、其他原因34例(包括大出血15例、恶病质15例、其他疾病4例);手术联合放化疗组死亡12例,占手术联合放化疗组的44.44%;放化疗组死亡39例,占放化疗组的76.47%。78例患者的1、3、5年OS率分别为57.7%、36.3%、27.2%,1、2、3年PFS率分别为49.5%、38.7%和32.6%,1、2、3年LCR分别为53.4%、40.0%、34.2%。其中手术联合放化疗组患者1、3、5年OS率分别为74.1%、50.1%、44.6%,放化疗组分别为49.0%、29.3%、12.8%,差异有统计学意义(χ²=5.142,P=0.023);手术联合放化疗组患者1、2、3年PFS率分别为62.1%、54.3%、44.4%,放化疗组分别为43.1%、30.6%、26.7%,差异无统计学意义(χ²=3.222,P=0.073);手术联合放化疗组患者1、2、3年LCR分别为69.8%、54.3%、44.4%,放化疗组分别为45.1%、32.9%、29.6%,差异无统计学意义(χ²=3.576,P=0.059)。单因素分析结果显示,肿瘤T分期(χ²=7.140,P=0.008)、N分期(χ²=4.493,P=0.034)、治疗方式(χ²=5.142,P=0.023)均为晚期下咽鳞状细胞癌患者OS的独立影响因素;T分期(χ²=5.807,P=0.016)和N分期(χ²=6.587,P=0.010)均为晚期下咽鳞状细胞癌患者PFS的独立影响因素。多因素分析结果显示,肿瘤T分期(HR=2.121,95%CI为1.142~3.938,P=0.017)、N分期(HR=2.088,95%CI为1.144~3.811,P=0.016)、治疗方式(HR=0.430,95%CI为0.226~0.815,P=0.010)均为晚期下咽鳞状细胞癌患者OS的独立预后因素;肿瘤T分期(HR=1.884,95%CI为1.011~3.510,P=0.046)、N分期(HR=1.904,95%CI为1.058~3.429,P=0.032)均为晚期下咽鳞状细胞癌患者PFS的独立预后因素。治疗期间手术联合放化疗组与放化疗组患者放射性咽炎[7.41%(2/27)vs.39.22%(20/51),χ²=8.821,P=0.003]和放射性皮炎[3.70%(1/27)vs.29.41%(15/51),χ=7.156,P=0.007]发生率差异均具有统计学意义,两组患者放射性口腔黏膜炎[11.11%(3/27)vs.17.65%(9/51),χ²=0.186,P=0.666]、骨髓抑制[37.04%(10/27)vs.50.98%(26/51),χ²=1.381,P=0.240]、咽部感染[11.11%(3/27)vs.5.88%(3/51),χ²=0.143,P=0.706]及气管瘘[7.41%(2/27)vs.0(0/51),P=0.117]等不良反应发生率比较,差异均无统计学意义。结论手术联合放化疗组患者的1、3、5年OS率高于放化疗组患者,且不良反应发生率低。肿瘤T分期、N分期、治疗方式均为晚期下咽鳞状细胞癌患者OS的独立预后因素,肿瘤T分期、N分期均为晚期下咽鳞状细胞癌患者PFS的独立预后因素。

关键词:下咽肿瘤,外科手术,化放疗,综合疗法,预后

Abstract:

ObjectiveTo compare the survival rate and adverse reactions of patients with advanced hypopharyngeal squamous cell carcinoma undergoing surgery combined with chemoradiotherapy, and to analyze the prognostic factors of patients.MethodsThe clinicopathologic data of 78 patients with advanced hypopharyngeal squamous cell carcinoma admitted to the Department of Radiation Oncology of the First Affiliated Hospital of Bengbu Medical University from August 2013 to December 2018 were retrospectively analyzed. The patients were divided into surgery combined with chemoradiotherapy group (n=27) and chemoradiotherapy group (n=51) according to different treatment methods. The median follow-up time was 46 months (20-84 months). The main observation indicators were overall survival (OS), progression-free survival (PFS) and local control rate (LCR). Cox regression model was used to analyze the prognostic factors.ResultsUntil July 31, 2020, 51 of the 78 patients with advanced hypopharyngeal squamous cell carcinoma died, including 6 cases of local recurrence, 11 cases of distant metastasis, and 34 cases of other causes (15 cases of hemorrhage, 15 cases of cachexia, and 4 cases of other diseases). In the surgery combined with chemoradiotherapy group, 12 patients died, accounting for 44.44%. In the chemoradiotherapy group, 39 patients died, accounting for 76.47%. The 1-, 3- and 5-year OS rates of 78 patients were 57.7%, 36.3% and 27.2% respectively, the 1-, 2- and 3-year PFS rates were 49.5%, 38.7% and 32.6% respectively, and the 1-, 2- and 3-year LCR were 53.4%, 40.0% and 34.2% respectively. The 1-, 3- and 5-year OS rates in the surgery combined with chemoradiotherapy group were 74.1%, 50.1% and 44.6%, and those in the chemoradiotherapy group were 49.0%, 29.3% and 12.8%, with a statistically significant difference (χ²=5.142,P=0.023). The 1-, 2- and 3-year PFS rates in the surgery combined with chemoradiotherapy group were 62.1%, 54.3% and 44.4%, and those in the chemoradiotherapy group were 43.1%, 30.6% and 26.7%, with no statistically significant difference (χ²=3.222,P=0.073). The 1-, 2- and 3-year LCR of the surgery combined with chemoradiotherapy group were 69.8%, 54.3% and 44.4%, and those in the chemoradiotherapy group were 45.1%, 32.9% and 29.6%, with no statistically significant difference (χ²=3.576,P=0.059). The results of univariate analysis showed that tumor T stage (χ²=7.140,P=0.008), N stage (χ²=4.493,P=0.034) and treatment method (χ²=5.142,P=0.023) were all independent influencing factors of the OS of patient with advanced hypopharyngeal squamous cell carcinoma; T stage (χ²=5.807,P=0.016) and N stage (χ²=6.587,P=0.010) were both independent influencing factors of PFS. The results of multivariate analysis showed that tumor T stage (HR=2.121, 95%CI: 1.142-3.938,P=0.017), N stage (HR=2.088, 95%CI: 1.144-3.811,P=0.016) and treatment method (HR=0.430, 95%CI: 0.226-0.815,P=0.010) were all independent prognostic factors of the OS of patients with advanced hypopharyngeal squamous cell carcinoma; T stage (HR=1.884, 95%CI: 1.011-3.510,P=0.046) and N stage (HR=1.904, 95%CI: 1.058-3.429,P=0.032) were both independent prognostic factors of PFS. During the treatment period, there were statistically significant differences in the incidences of radioactive pharyngitis [7.41% (2/27)vs.39.22%(20/51),χ²=8.821,P=0.003] and radioactive dermatitis [3.70% (1/27)vs.29.41%(15/51),χ²=7.156,P=0.007] between the surgery combined with chemoradiotherapy group and the chemoradiotherapy group. However, there were no statistically significant differences in the incidences of radioactive oral mucositis [11.11% (3/27)vs.17.65%(9/51),χ²=0.186,P=0.666], bone marrow suppression [37.04% (10/27)vs.50.98%(26/51),χ²=1.381,P=0.240], pharynx infection [11.11% (3/27)vs.5.88%(3/51),χ²=0.143,P=0.706] and tracheal fistula [7.41% (2/27)vs.0 (0/51),P=0.117] between the two groups.ConclusionThe 1-, 3- and 5-year OS rates in the surgery combined with chemoradiotherapy group are higher than those in the chemoradiotherapy group, and the incidences of adverse reactions are low. T stage, N stage and treatment method are independent prognostic factors for OS of advanced hypopharyngeal squamous cell carcinoma patients, while T stage and N stage are independent prognostic factors for PFS.

Key words:Hypopharyngeal neoplasms,Surgical procedures, operative,Chemoradiotherapy,Com-bined modality therapy,Prognosis

程翠, 孙利, 蔡丰, 江浩, 孙谦. 手术联合放化疗治疗晚期下咽癌的生存及安全性评价[J]. 国际肿瘤学杂志, 2021, 48(2): 80-85.

Cheng Cui, Sun Li, Cai Feng, Jiang Hao, Sun Qian. Survival and safety evaluation of surgery combined with chemoradiotherapy for advanced hypopharyngeal carcinoma[J]. Journal of International Oncology, 2021, 48(2): 80-85.

图/表5

表1

78例晚期下咽鳞状细胞癌患者一般临床资料(例)"

一般临床特征	例数	手术联合放化疗组 (n=27)	放化疗组 (n=51)	χ²值	P值
性别
男	74	27	47	2.232	0.135
女	4	0	4
年龄(岁)
<65	39	14	25	0.057	0.812
≥65	39	13	26
吸烟史
是	33	9	24	1.363	0.243
否	45	18	27
饮酒史
是	32	8	24	2.217	0.137
否	46	19	27
TNM分期
Ⅲ期	31	10	21	0.126	0.722
Ⅳ期	47	17	30
亚解剖部位
梨状窝	62	22	40
咽后壁	10	3	7	0.119	0.942
环后区	6	2	4
分化程度
低分化	36	12	24
中分化	31	14	17	4.716	0.095
高分化	11	1	10
KPS评分(分)
80~89	33	8	25	2.719	0.099
90~100	45	19	26

表1

图1

表2

影响78例晚期下咽鳞状细胞癌患者OS的单因素分析(%)"

影响因素	例数	1年 OS率	3年 OS率	5年 OS率	χ²值	P值
性别
男	74	59.5	36.8	27.4	1.027	0.311
女	4	25.0	25.0	25.0
年龄(岁)
<65	39	56.4	35.9	35.9	0.127	0.721
≥65	39	59.0	36.6	19.0
吸烟史
是	33	60.6	26.1	26.1	0.317	0.573
否	45	55.6	43.7	30.1
饮酒史
是	32	53.1	23.3	23.3	1.284	0.257
否	46	60.9	45.0	31.5
T分期
T_1-2	30	73.3	49.5	49.5	7.140	0.008
T_3-4	48	47.9	28.1	14.3
N分期
N_0-1	33	72.7	50.1	36.4	4.493	0.034
N_2-3	45	46.7	25.7	21.4
治疗方式
手术联合放化疗	27	74.1	50.1	44.6	5.142	0.023
放化疗	51	49.0	29.3	12.8
亚解剖部位
梨状窝	62	61.3	39.6	26.6
咽后壁	10	40.0	20.0	20.0	0.810	0.667
环后区	6	50.0	33.3	33.3
影响因素	例数	1年 OS率	3年 OS率	5年 OS率	χ²值	P值
分化程度
低分化	36	58.3	36.1	30.1
中分化	31	58.1	33.9	19.4	0.382	0.826
高分化	11	54.5	45.5	45.5

表2

表3

影响78例晚期下咽鳞状细胞癌患者PFS的单因素分析(%)"

影响因素	例数	1年 PFS率	2年 PFS率	3年 PFS率	χ²值	P值
性别
男	74	50.8	39.4	32.8	0.687	0.407
女	4	25.0	25.0	25.0
年龄(岁)
<65	39	47.6	39.2	34.3	0.006	0.936
≥65	39	51.3	38.5	31.5
吸烟史
是	33	48.5	36.4	27.3	0.112	0.378
否	45	50.2	40.7	37.0
饮酒史
是	32	40.6	34.4	24.6	0.976	0.323
否	46	55.8	41.8	38.3
T分期
T_1-2	30	65.7	54.7	48.7	5.807	0.016
T_3-4	48	39.6	29.2	23.3
N分期
N_0-1	33	72.7	54.2	45.9	6.587	0.010
N_2-3	45	32.0	27.1	22.6
治疗方式
手术联合放化疗	27	62.1	54.3	44.4	3.222	0.073
放化疗	51	43.1	30.6	26.7
亚解剖部位
梨状窝	62	52.6	42.4	33.9
咽后壁	10	40.0	20.0	20.0	1.064	0.588
环后区	6	50.0	33.3	33.3
分化程度
低分化	36	55.6	40.9	30.7
中分化	31	43.6	33.5	22.8	0.787	0.675
高分化	11	45.5	45.5	45.5

表3

不良反应	手术联合放化疗组 (n=27)	放化疗组 (n=51)	χ²值	P值
放射性咽炎	2(7.41)	20(39.22)	8.821	0.003
放射性口腔黏膜炎	3(11.11)	9(17.65)	0.186	0.666
放射性皮炎	1(3.70)	15(29.41)	7.156	0.007
骨髓抑制	10(37.04)	26(50.98)	1.381	0.240
咽部感染	3(11.11)	3(5.88)	0.143	0.706
气管瘘	2(7.41)	0(0)	-	0.117

表4

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