Clinical significance of circulating tumor cells in radical radiotherapy for esophageal cancer
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摘要:目的
探讨食管癌患者循环肿瘤细胞(CTCs)与临床特征及预后的相关性。
方法选取南通市通州区人民医院2019年8月11日—2021年3月4日收治的114例食管鳞癌患者为研究对象,采用免疫磁珠阴性富集联合免疫荧光原位杂交技术检测CTCs。收集患者临床资料,结合其TNM分期、性别、年龄、肿瘤位置等临床特征进行统计学分析; 比较50例根治性放疗患者在放疗前后的CTCs水平,分析CTCs水平与近期缓解率和无进展生存期(PFS)的关系。
结果114例食管鳞癌患者CTCs阳性率与年龄、性别、肿瘤位置无相关性(P>0.05), 与肿瘤T分期、N分期、M分期以及临床分期有相关性(P<0.05或P<0.01)。50例患者放疗前的CTCs阳性率为62.00%(31/50), 放疗后的CTCs阳性率为52.00%(26/50), 差异无统计学意义(χ2=1.020, P=0.313)。Kaplan-Meier方法绘制生存曲线的结果显示,放疗前CTCs阴性患者PFS为18.62个月(95%CI: 15.24~21.99), 高于CTCs阳性患者的13.84个月(95%CI: 10.01~17.68), 差异有统计学意义(P=0.048)。放疗后CTCs阴性患者PFS为19.58个月(95%CI: 16.51~22.67), 高于CTCs阳性患者的12.13个月(95%CI: 7.94~16.32), 差异有统计学意义(P=0.003)。多因素Cox回归分析显示,肿瘤临床分期、放疗后CTCs是食管鳞癌患者的独立预后因子(P<0.05)。
结论CTCs是食管鳞癌患者病情进展评估及放疗后预后评价的重要指标。
Abstract:ObjectiveTo explore the correlations of circulating tumor cells (CTCs) with clinical features and prognosis in patients with esophageal cancer.
MethodsA total of 114 patients with esophageal squamous cell carcinoma in Tongzhou District People's Hospital of Nantong City from August 11, 2019 to March 4, 2021 were selected as research objects, and CTCs were detected by immunomagnetic bead negative enrichment combined with immunofluorescence in situ hybridization. The clinical data of patients were collected and statistically analyzed in combination with clinical features such as TNM staging, gender, age and tumor location; the level of CTCs before and after radiotherapy was compared in 50 patients with radical radiotherapy, and the correlations of CTCs level with short-term remission rate and progression free survival (PFS) were analyzed.
ResultsIn 114 patients with esophageal squamous cell carcinoma, positive rate of CTCs had no correlations with age, gender and tumor location (P > 0.05), but was correlated with T staging, N staging, M staging and clinical stages (P < 0.05 or P < 0.01). The positive rate of CTCs in 50 patients was 62.00% (31/50) before radiotherapy and 52.00% (26/50) after radiotherapy, and there was no significant difference before and after radiotherapy (χ2=1.020, P=0.313). The survival curve drawn by Kaplan-Meier method showed that the PFS of patients negative for CTCs before radiotherapywas 18.62 months (95%CI, 15.24 to 21.99), which was significantly higher than 13.84 months (95%CI, 10.01 to 17.68) of patients positive for CTCs before radiotherapy(P=0.048). After radiotherapy, the PFS of patients negative for CTCs was 19.58 months (95%CI, 16.51 to 22.67), which was significantly higher than 12.13 months (95%CI, 7.94 to 16.32) of patients positive for CTCs (P=0.003). Multivariate Cox regression analysis showed that tumor clinical stages and CTCs after radiotherapy were the independent prognostic factors of patients with esophageal squamous cell carcinoma (P < 0.05).
ConclusionCTCs i s an important index in evaluating the progress of disease and prognostic assessment after radiotherapyin patients with esophageal squamous cell carcinoma.
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表 1 114例食管鳞癌患者CTCs与临床病理特征关系
临床病理特征 分类 n CTCs 阳性率/% χ2 P 阴性 阳性 年龄 <60岁 29 15 14 48.28 1.476 0.224 ≥60岁 85 33 52 61.18 性别 男 88 34 54 61.36 1.905 0.168 女 26 14 12 46.15 肿瘤位置 上段 31 17 14 45.16 3.810 0.149 中段 56 23 33 58.93 下段 27 8 19 70.37 T分期 T1 17 12 5 29.41 9.682 0.021 T2 40 18 22 55.00 T3 38 14 24 63.16 T4 19 4 15 78.95 N分期 N0 42 27 15 35.71 14.153 0.001 N1 35 12 23 65.71 N2 37 9 28 75.68 N3 0 0 0 0 M分期 M0 104 47 57 54.81 4.635 0.031 M1 10 1 9 90.00 临床分期 Ⅰ期 27 21 6 22.22 24.380 0.001 Ⅱ期 32 15 17 53.13 Ⅲ期 45 11 34 75.56 Ⅳ期 10 1 9 90.00 表 2 50例食管鳞癌患者CTCs与放疗后近期疗效的关系
时点 CTCs分类 n 疗效评价 RR/% χ2 P CR+PR SD 放疗前 阴性 19 16 3 84.21 4.529 0.033 阳性 31 17 14 54.84 放疗后 阴性 24 20 4 83.33 6.179 0.013 阳性 26 13 13 50.00 放疗前后变化 放疗前后均为阳性 22 13 9 59.09 11.644 0.009 放疗前阳性而放疗后阴性 9 8 1 88.89 放疗前阴性而放疗后阳性 4 0 4 0 放疗前后均为阴性 15 12 3 80.00 表 3 食管鳞癌患者放疗后PFS的COX回归分析
预后因素 回归系数 Wald P OR 95%CI 下限 上限 年龄 -0.287 0.112 0.737 0.750 0.140 4.027 性别 0.286 0.166 0.684 1.331 0.337 5.258 T分期 -0.368 0.319 0.572 0.692 0.193 2.481 N分期 -0.184 0.074 0.786 0.832 0.220 3.141 临床分期 1.674 4.743 0.029 5.334 1.182 24.063 放疗前CTCs 0.183 0.042 0.838 1.201 0.207 6.966 放疗后CTCs 2.027 5.274 0.022 7.592 1.346 42.820 -
[1] BRAY F, FERLAY J, SOERJOMATARAM I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA a Cancer JClin, 2018, 68(6): 394-424. doi: 10.3322/caac.21492
[2] ZHANG S W, SUN K X, ZHENG R S, et al. Cancer incidence and mortality in China, 2015[J]. Journal of the National Cancer Center, 2021, 1(1): 2-11. doi: 10.1016/j.jncc.2020.12.001
[3] MATSUSHITA D, ARIGAMI T, OKUBO K, et al. The Diagnostic and Prognostic Value of a Liquid Biopsy for Esophageal squamous cell carcinoma: A Systematic Review and Meta-Analysis[J]. Cancers, 2020, 12(10): 3070. doi: 10.3390/cancers12103070
[4] CASTRO-GINER F, ACETO N. Tracking cancer progression: from circulating tumor cells to metastasis[J]. Genome Med, 2020, 12(1): 31. doi: 10.1186/s13073-020-00728-3
[5] ZHANG P, ZHOU H, LU K, et al. Circulating tumor cells in the clinical cancer diagnosis[J]. ClinTranslOncol, 2020, 22(3): 279-282.
[6] 中国医师协会放射肿瘤治疗医师分会, 中华医学会放射肿瘤治疗学分会, 中国抗癌协会肿瘤放射治疗专业委员会. 中国食管癌放射治疗指南(2019年版)[J]. 国际肿瘤学杂志, 2019, 46(7): 385-398. doi: 10.3760/cma.j.issn.1673-422X.2019.07.001 [7] ARAS M, ERDIL T Y, DANE F, et al. Comparison of WHO, RECIST 1. 1, EORTC, and PERCIST criteria in the evaluation of treatment response in malignant solid tumors[J]. NuclMedCommun, 2016, 37(1): 9-15.
[8] SMYTHEC, LAGERGRENJ, FITZGERALDRC, et al. Oesophagealcancer[J]. The Lancet, 2017, 390(10110): 2383-2396. doi: 10.1016/S0140-6736(17)31462-9
[9] YE Q W, LING S B, ZHENG S S, et al. Liquid biopsy in hepatocellular carcinoma: circulating tumor cells and circulating tumor DNA[J]. Mol Cancer, 2019, 18(1): 114. doi: 10.1186/s12943-019-1043-x
[10] BOYA M, CHUCH, LIU R X, et al. Circulating Tumor Cell Enrichment Technologies[J]. TumorLiqBiopsies, 2020, 215: 25-55.
[11] MATSUSHITA D, UENOSONO Y, ARIGAMI T, et al. Clinical significance of circulating tumor cells in peripheral blood of patients with esophageal squamous cell carcinoma[J]. Ann Surg Oncol, 2015, 22(11): 3674-3680. doi: 10.1245/s10434-015-4392-8
[12] LI SP, GUAN QL, ZHAO D, et al. Detection of Circulating Tumor Cells by Fluorescent Immunohistochemistry in Patients with Esophageal Squamous Cell Carcinoma: Potential Clinical Applications[J]. Med Sci Monit, 2016, 22: 1654-1662. doi: 10.12659/MSM.898335
[13] QIAO Y, LI J, SHI C, et al. Prognostic value of circulating tumor cells in the peripheral blood of patients with esophageal squamous cell carcinoma[J]. Onco Targets Ther, 2017, 10: 1363-1373. doi: 10.2147/OTT.S129004
[14] OZPISKIN O M, ZHANG L, LIJJ. Immune targets in the tumor microenvironment treated by radiotherapy[J]. Theranostics, 2019, 9(5): 1215-1231. doi: 10.7150/thno.32648
[15] ASHRAFIZADEH M, FARHOOD B, ELEOJO MUSA A, et al. Abscopal effect in radioimmunotherapy[J]. IntImmunopharmacol, 2020, 85: 106663.
[16] LIANG D H, HALL C, ANTHONY L. Circulating Tumor Cells in Breast Cancer[J]. Recent Results Cancer Res, 2020, 215: 127-145.
[17] MALY V, MALY O, KOLOSTOVA K, et al. Circulating Tumor Cells in Diagnosis and Treatment of Lung Cancer[J]. In Vivo, 2019, 33(4): 11571.
[18] PHUNGTH, SANJEEVG, NGUYENTB, et al. Emerging Role of Circulating Tumor Cells in Gastric Cancer[J]. Cancers, 2020, 12(3), 695. doi: 10.3390/cancers12030695
[19] WOESTEMEIER A, HARMS-EFFENBERGER K, KARSTENS K F, et al. Clinical Relevance of Circulating Tumor Cells in Esophageal Cancer Detected by a Combined MACS Enrichment Method[J]. Cancers, 2020, 12(3): 718. doi: 10.3390/cancers12030718
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期刊类型引用(1)
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