TPF方案同步IMRT治疗对中晚期食管癌患者免疫功能及生存预后的影响

doi:10.3760/cma.j.cn371439-20210420-00013

摘要/Abstract

摘要：

目的研究多西他赛、顺铂和氟尿嘧啶联合化疗(TPF方案)同步调强放疗(IMRT)对中晚期食管癌患者免疫功能及生存预后的影响。方法筛选2015年6月至2017年12月河北省退役军人总医院收治的中晚期食管癌患者93例,采用随机信封法分为2组,观察组(47例)给予TPF方案同步IMRT,对照组(46例)给予PF方案(顺铂联合氟尿嘧啶)同步IMRT。治疗结束后的1个月内复查食管钡餐、胸部及上腹部CT,评估其近期疗效,并比较两组治疗前后免疫功能情况;绘制Kaplan-Meier生存曲线,以总生存期(OS)评估其远期疗效;收集两组患者不良反应发生情况,评估其安全性。结果治疗后观察组T细胞亚群CD8⁺水平高于对照组[(33.55±4.46)% vs. (29.06±3.61)%,P<0.05],而CD3⁺[(51.29±5.22)% vs. (56.04±6.10)%,P<0.05]、CD4⁺[(28.27±3.63)% vs. (30.35±3.52)%,P<0.05]及CD4⁺/CD8⁺ (0.84±0.25 vs. 1.04±0.08,P<0.05)水平低于对照组。观察组近期治疗有效率达82.98%(39/47),而对照组的有效率仅63.04%(29/46),两组差异具有统计学意义(χ²=4.70,P=0.030)。观察组的中位OS为25.3个月(95%CI为17.9~26.1),对照组为18.2个月(95%CI为14.4~25.5),差异具有统计学意义(χ²=3.28,P=0.038)。两组患者随访期间的不良反应主要为恶心/呕吐、疲乏、食欲不振、血液学毒性、食管炎和肺炎等,大多为1~2级,给予对症处理或结束治疗即可消失;相较于对照组,观察组恶心/呕吐(46.81% vs. 78.26%,χ²=9.80,P=0.002)、食欲不振(44.86% vs. 71.74%,χ²=6.99,P=0.008)、白细胞减少(36.96% vs. 73.91%,χ²=13.37,P<0.001)、食管炎(61.70% vs. 82.61%,χ²=5.05,P=0.025)不良反应发生率更低。结论 TPF同步IMRT的治疗方案有效性高且不良反应低,可作为中晚期食管癌患者生存预后改善的有效方案。

关键词: 食管肿瘤, 放射疗法, 调强适形, 多西他赛, 免疫功能, 预后

Abstract:

Objective To study the effects of docetaxel, cisplatin and fluorouracil (TPF) regimen simultaneous intensity modulated radiotherapy (IMRT) on immune function and survival prognosis of patients with advanced esophageal cancer. Methods A total of 93 patients with advanced esophageal cancer were screened in Hebei Veterans General Hospital from June 2015 to December 2017, and were divided into two groups using randomized envelope method. The observation group (47 cases) was given synchronous TPF regimen and IMRT, and the control group (46 cases) was given synchronous PF regimen (cisplatin combined with fluorouracil) and IMRT. Esophageal barium meal, chest and upper abdominal CT were reviewed within 1 month after treatment to assess the short-term efficacy and compare the immune function of the two groups before and after treatment. Kaplan-Meier survival curve was plotted to evaluate the long-term efficacy based on overall survival (OS). The incidence of adverse reactions in the two groups was collected to evaluate their safety. Results After treatment, the T cell subgroup CD8⁺ level of the observation group was higher than that of the control group [(33.55±4.46)% vs. (29.06±3.61)%, P<0.05], while CD3⁺[(51.29±5.22)% vs. (56.04±6.10)%, P<0.05], CD4⁺ [(28.27±3.63)% vs. (30.35±3.52)%, P<0.05] and CD4⁺/CD8⁺ (0.84±0.25 vs. 1.04±0.08, P<0.05) levels were lower than those of the control group. The effective rate of recent treatment in the observation group was 82.98% (39/47), while the effective rate in the control group was only 63.04% (29/46), with a statistically significant difference (χ²=4.70, P=0.030). The median OS of the observation group was 25.3 months (95%CI: 17.9-26.1), and that of the control group was 18.2 months (95%CI: 14.4-25.5), with a statistically significant difference (χ ²=3.28, P=0.038). Adverse reactions during the follow-up period of the two groups of patients were mainly nausea/vomiting, fatigue, anorexia, hematological toxicity, esophagitis and pneumonia, etc., which were mostly grade 1-2, and disappeared after symptomatic treatment or termination of treatment. Compared with the control group, the incidence of nausea/vomiting (46.81% vs. 78.26%, χ ²=9.80, P=0.002), anorexia (44.86% vs. 71.74%, χ ²=6.99, P=0.008), leukopenia (36.96% vs. 73.91%, χ ²=13.37, P<0.001) and esophagitis (61.70% vs. 82.61%, χ ²=5.05, P=0.025) adverse reactions was lower in the observation group. Conclusion TPF combined with IMRT has high efficacy and low adverse reactions, which can be used as an effective treatment to improve the survival prognosis of patients with advanced esophageal cancer.

Key words: Esophageal neoplasms, Radiotherapy, intensity-modulated, Docetaxel, Immune function, Prognosis

耿惠, 胡锋超, 路洪超, 郭军岗, 齐增平. TPF方案同步IMRT治疗对中晚期食管癌患者免疫功能及生存预后的影响[J]. 国际肿瘤学杂志, 2022, 49(2): 84-88.

Geng Hui, Hu Fengchao, Lu Hongchao, Guo Jungang, Qi Zengping. Effects of TPF regimen and IMRT on immune function and survival prognosis of patients with advanced esophageal cancer[J]. Journal of International Oncology, 2022, 49(2): 84-88.

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参考文献 17

[1]	Wu YF, Chu SC, Chang BS, et al. Hematologic markers as prognostic factors in nonmetastatic esophageal cancer patients under concurrent chemoradiotherapy[J]. Biomed Res Int, 2019, 2019:1263050. DOI: 10.1155/2019/1263050. doi: 10.1155/2019/1263050
[2]	郑臻, 朱兆峰. 超声内镜相关技术在早期食管癌诊断中的应用[J]. 国际肿瘤学杂志, 2021, 48(3): 176-179. DOI: 10.3760/cma.j.cn371439-20200630-00035. doi: 10.3760/cma.j.cn371439-20200630-00035
[3]	Jung MK, Schmidt T, Chon SH, et al. Current surgical treatment standards for esophageal and esophagogastric junction cancer[J]. Ann N Y Acad Sci, 2020, 1482(1): 77-84. DOI: 10.1111/nyas.14454. doi: 10.1111/nyas.14454
[4]	陈赟, 艾沓杉, 夏怡, 等. 紫杉醇联合氟尿嘧啶同期放疗治疗初治局部晚期食管鳞癌患者的Ⅱ期临床研究[J]. 中国癌症杂志, 2016, 26(11): 926-931. DOI: 10.19401/j.cnki.1007-3639.2016.11.008. doi: 10.19401/j.cnki.1007-3639.2016.11.008
[5]	Cascone T, Sepesi B, Lin HY, et al. A phase Ⅰ/Ⅱ study of neoadjuvant cisplatin, docetaxel, and nintedanib for resectable non-small cell lung cancer[J]. Clin Cancer Res, 2020, 26(14): 3525-3536. DOI: 10.1158/1078-0432.CCR-19-4180. doi: 10.1158/1078-0432.CCR-19-4180 pmid: 32193228
[6]	戴婷婷, 王万伟, 仝宇梭, 等. 多西他赛联合顺铂同步放化疗和单纯放疗治疗老年非手术食管鳞癌的临床疗效分析[J]. 实用癌症杂志, 2019, 34(3): 417-420. DOI: 10.3969/j.issn.1001-5930.2019.03.019. doi: 10.3969/j.issn.1001-5930.2019.03.019
[7]	Xue J, Jia E, Ren N, et al. Identification of prognostic miRNA biomarkers for esophageal cancer based on The Cancer Genome Atlas and Gene Expression Omnibus[J]. Medicine (Baltimore), 2021, 100(7): e24832. DOI: 10.1097/MD.0000000000024832. doi: 10.1097/MD.0000000000024832
[8]	Triantafyllou T, Wijnhoven BPL. Current status of esophageal cancer treatmen[J]. Chin J Cancer Res, 2020, 32(3): 271-286. DOI: 10.21147/j.issn.1000-9604.2020.03.01. doi: 10.21147/j.issn.1000-9604.2020.03.01
[9]	周平, 陈伟思, 张爽, 等. 紫杉醇同期放疗治疗鼻咽癌肝转移的疗效观察[J]. 国际肿瘤学杂志, 2019, 46(6): 327-330. DOI: 10.3760/cma.j.issn.1673-422X.2019.06.002. doi: 10.3760/cma.j.issn.1673-422X.2019.06.002
[10]	Zhang Y, Zhang W, Wang Y, et al. Emerging nanotaxanes for can-cer therapy[J]. Biomaterials, 2021, 272:120790. DOI: 10.1016/j.biomaterials.2021.120790. doi: 10.1016/j.biomaterials.2021.120790
[11]	Maeda O, Ando Y. Recent progress of chemotherapy and biomarkers for gastroesophageal cancer[J]. World J Gastrointest Oncol, 2019, 11(7): 518-526. DOI: 10.4251/wjgo.v11.i7.518. doi: 10.4251/wjgo.v11.i7.518
[12]	中国抗癌协会多原发和不明原发肿瘤专业委员会. 中国紫杉类药物剂量密集化疗方案临床应用专家共识[J]. 中国癌症杂志, 2019, 29(11): 910-920. DOI: 10.19401/j.cnki.1007-3639.2019.11.011. doi: 10.19401/j.cnki.1007-3639.2019.11.011
[13]	de Weger VA, Beijnen JH, Schellens JH. Cellular and clinical pharmacology of the taxanes docetaxel and paclitaxel—a review[J]. Anticancer Drugs, 2014, 25(5): 488-494. DOI: 10.1097/CAD.0000000000000093. doi: 10.1097/CAD.0000000000000093
[14]	杨雄, 金泓宇, 宫丽娜, 等. 以多西他赛为基础的新辅助化疗在前列腺癌中的应用进展[J]. 临床泌尿外科杂志, 2021, 36(2): 120-125. DOI: 10.13201/j.issn.1001-1420.2021.02.008. doi: 10.13201/j.issn.1001-1420.2021.02.008
[15]	Lin L, Kane N, Kobayashi N, et al. High-dose per fraction radiotherapy induces both antitumor immunity and immunosuppressive responses in prostate tumors[J]. Clin Cancer Res, 2021, 27(5): 1505-1515. DOI: 10.1158/1078-0432.CCR-20-2293. doi: 10.1158/1078-0432.CCR-20-2293 pmid: 33219015
[16]	丁宏, 卢惠茹, 蒋昊. 多西他赛及其新剂型的临床应用进展[J]. 医学理论与实践, 2019, 32(14): 2165-2167. DOI: 10.19381/j.issn.1001-7585.2019.14.010. doi: 10.19381/j.issn.1001-7585.2019.14.010
[17]	李玉, 耿晓萌, 李文文, 等. 低剂量多西他赛周疗同步放疗治疗局部晚期食管癌的疗效与安全性分析[J]. 现代肿瘤医学, 2021, 29(5): 787-789. DOI: 10.3969/j.issn.1672-4992.2021.05.015. doi: 10.3969/j.issn.1672-4992.2021.05.015

一般资料	观察组 (n=47)	对照组 (n=46)	t/χ²值	P值
年龄(岁)	49.83±5.36	48.77±5.42	0.99	0.346
性别
男	27(57.45)	20(43.48)	1.82	0.178
女	20(42.55)	26(56.52)
肿瘤部位
胸上及颈段	14(29.79)	11(23.91)
胸中段	19(40.43)	25(54.35)	1.83	0.400
胸下段	14(29.79)	10(21.74)
分化程度
高、中分化	30(63.83)	36(78.26)	2.35	0.125
低、未分化	17(36.17)	10(21.74)
TNM分期
Ⅱ期	15(31.91)	21(45.65)	1.85	0.174
Ⅲ期	32(68.09)	25(54.35)

T细胞亚群	观察组(n=47)				对照组(n=46)
T细胞亚群	治疗前	治疗后	t值	P值	治疗前	治疗后	t值	P值
CD3⁺(%)	61.23±6.63	51.29±5.22^a	8.02	<0.001	60.45±6.47	56.04±6.10	3.38	0.001
CD4⁺(%)	33.40±4.18	28.27±3.63^a	6.31	<0.001	32.78±4.01	30.35±3.52	3.10	0.003
CD8⁺(%)	25.36±3.24	33.55±4.46^a	-10.11	<0.001	25.10±3.13	29.06±3.61	-5.66	<0.001
CD4⁺/CD8⁺	1.32±0.30	0.84±0.25^a	8.37	<0.001	1.30±0.31	1.04±0.08	5.56	<0.001