[an error occurred while processing this directive] | [an error occurred while processing this directive]
Radiotherapy progress in elderly patients with unresectable esophageal carcinoma
Yang Xu, Liang Jun
Department of Radiation Oncology,National Cancer Center/Cancer Hospital,Chinese Academy of Medical Sciences,Peking Union Medical College,Beijing 100021,China
Abstract As the fourth leading cause of cancer death for years,esophageal carcinoma yields a high morbidity in China. In an aging society,the quantity of elderly patients with esophageal carcinoma is ever increasing. However,elderly patients have been excluded in most studies due to more comorbidities,lower performance status grade,worse therapeutic tolerance and other clinical features. Although clinical prognosis of esophageal carcinoma patients has been improved in the past decades, the clinical efficacy in the treatment of esophageal carcinoma in elderly patients is still unsatisfactory. Current options should be combined with novel therapeutic srategies to enhance the clinical efficacy. In this article, the clinical efficacy and adverse events of radiotherapy, radiochemotherapy, targeted therapy or immunotherapy in treating elderly patients with unresectable esophageal carcinoma were retrospectively analyzed.
Yang Xu,Liang Jun. Radiotherapy progress in elderly patients with unresectable esophageal carcinoma[J]. Chinese Journal of Radiation Oncology, 2018, 27(3): 316-322.
Yang Xu,Liang Jun. Radiotherapy progress in elderly patients with unresectable esophageal carcinoma[J]. Chinese Journal of Radiation Oncology, 2018, 27(3): 316-322.
[1] Chen WQ,Zheng RS,Baade PD,et al. Cancer statistics in China,2015[J].CA Cancer J Clin,2016,66(2):115-132.DOI:10.3322/caac.21338. [2] Steyerberg EW,Neville B,Weeks JC,et al. Referral patterns,treatment choices,and outcomes in locoregional esophageal cancer:a population-based analysis of elderly patients[J].J Clin Oncol,2007,25(17):2389-2396.DOI:10.1200/JCO.2006.09.7931. [3] Herskovic A,Martz K,Al-Sarraf M,et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus[J].N Engl J Med,1992,326(24):1593-1598.DOI:10.1056/NEJM199206113262403. [4] 肖泽芬,章众,张红志,等.用三维治疗计划系统评估食管癌常规放射治疗中肿瘤剂量的分布[J].中华放射肿瘤学杂志,2004,13(4):273-277.DOI:10.3760/j.issn:1004-4221.2004.04.008. Xiao ZF,Zhang Z,Zhang HZ,et al. Evaluation of tumor dose distribution in conventional radiotherapy for esophageal cancer using three-dimensional treatment planning system[J].Chin J Radiat Oncol,13(4):273-277.DOI:10.3760/j.issn:1004-4221.2004.04.008. [5] Yamada H,Yokoyama T,Ogiwara M,et al. Radiation therapy of carcinoma of the esophagus in the aged—its results and problems[J].Nihon RonenIgakkai Zasshi,1994,31(3):237-243. [6] Hishikawa Y,Kurisu K,Taniguchi M,et al. Radiotherapy for carcinoma of the esophagus in patients aged eighty or older[J].Int J Radiat Oncol Biol Phys,1991,20(4):685-688.DOI:10.1016/0360-3016(91)90009-S. [7] Yin WB.Radiotherapy of carcinoma of oesophagus in china[J].Chin Med J,1997,110(4):289-293. [8] Guzel Z,Bedford JL,Childs PJ,et al. A comparison of conventionaland conformalradiotherapy of the oesophagus:work in progress[J].Br J Radiol,1998,71(805):1076-1082.DOI:10.1259/bjr.71.850.10211069. [9] Bedford JL,Viviers L,Guzel Z,et al. A quantitative treatment planning study evaluating the potential of dose escalation in conformal radiotherapy of the oesophagus[J].Radiother Oncol,2000,57(2):183-193.DOI:10.1016/S0167-8140(00)00258-9. [10] 韦淦宝.50例老年食管癌三维适形放疗的远期疗效分析[J].中国医疗前沿,2013,8(12):72-73.DOI:10.3969/j.issn.1673-5552.2013.12.0053. Wei GB. 50 cases of senile esophageal forward curative effect analysis of three dimensional conformal radiotherapy[J]. Chin Med Front,2013,8(12):72-73.DOI:10.3969/j.issn.1673-5552.2013.12.0053. [11] 张清琴,崔艳慧,杨军,等.老年Ⅰ~Ⅱ a期食管癌患者三维适形与普通放疗的疗效比较[J].中国老年学杂志,2014,34(13):3564-3566.DOI:10.3969/j.issn.1005-9202.2014.13.024. Zhang QQ,Cui YH,Yanbg J,et al. Elderly Ⅰ— Ⅱ a period in patients with esophageal three-dimensional conformal compared with ordinary radiotherapy curative effect[J].Chin J Gerontol,2014,34(13):3564-3566.DOI:10.3969/j.issn.1005-9202.2014.13.024. [12] 罗志强,黄燕,胡小燕.三维适形放疗治疗老年Ⅱ a期及以上食管癌的临床效果[J].中国当代医药,2014,21(34):39-40,46. Luo ZQ,Huang Y,Hu XY.Clinical effect of three-dimensional conformal radiotherapy on the treatment of Ⅱ a and above esophageal cancer[J].Chin Contemp Med,2014,21(34):39-40,46. [13] 杜宇,郝艳坤,王涓.老年食管癌患者放射治疗的临床分析[J].医学综述,2014,20(20):3824-3826.DOI:10.3969/j.issn.1006-2084.2014.20.073. Du Y,Hao YK,Wang J.Clinical analysis of radiotherapy for elderly patients with esophageal cancer[J].Med Eev,2014,20(20):3824-3826.DOI:10.3969/j.issn.1006-2084.2014.20.073. [14] 汪超,彭万仁,汤晓伟,等.75岁以上老年食管癌适形放疗疗效分析[J].现代肿瘤医学,2016,24(14):2240-2243.DOI:10.3969/j.issn.1672-4992.2016.14.019. Wang C,Peng WR,Tang XW,et al. Clinical analysis of conformal radiotherapy of esophageal cancer in aged 75 and older[J].Mod Oncol Med,2016,24(14):2240-2243.DOI:10.3969/j.issn.1672-4992.2016.14.019. [15] 李金利,周菊英,符天晓,等.老年食管癌三维适形放疗长期疗效及预后因素分析[J].中国老年学杂志,2014,34(19):5397-5399.DOI:10.3969/j.issn.1005-9202.2014.19.031. Li JG,Zhou JY,Fu TX,et al. Analysis of long-term efficacy and prognostic factors of three-dimensional conformal radiotherapy for aged esophageal cancer[J].J Chin Gerontol,2014,34(19):5397-5399.DOI:10.3969/j.issn.1005-9202.2014.19.031. [16] Chandra A,Guerrero TM,Liu HH,et al. Feasibility of using intensity-modulated radiotherapy to improve lung sparing in treatment planning for distal esophageal cancer[J].Radiother Oncol,2005,77(3):247-253.DOI:10.1016/j.radonc.2005.10.017. [17] Nutting CM,Bedford JL,Cosgrove VP,et al. A comparison of conformal and intensity-modulated techniques for oesophageal radiotherapy[J].Radiother Oncol,2001,61(2):157-163.DOI:10.1016/S0167-8140(01)00438-8. [18] Wu VWC,Sham JST,Kwong DLW.Inverse planning in three-dimensional conformal and intensity-modulated radiotherapy of mid-thoracic oesophageal cancer[J].BrJRadiol,2004,77(919):568-572.DOI:10.1259/bjr/19972578. [19] Fenkell L,Kaminsky I,Breen S,et al. Dosimetric comparison of IMRT vs.3D conformal radiotherapy in the treatment of cancer of the cervical esophagus[J].Radiother Oncol,2008,89(3):287-291.DOI:10.1016/j.radonc.2008.08.008. [20] Wu VWC,Kwong DLW,Sham JST.Target dose conformity in 3-dimensional conformal radiotherapy and intensity modulated radiotherapy[J].Radiother Oncol,2004,71(2):201-206.DOI:10.1016/j.radonc.2004.03.004. [21] Chen YJ,Liu A,Han CH,et al. Helical tomotherapy for radiotherapy in esophageal cancer:a preferred plan with better conformal target coverage and more homogeneous dose distribution[J].Med Dosim,2007,32(3):166-171.DOI:10.1016/j.meddos.2006.12.003. [22] Kole TP,Aghayere O,Kwah J,et al. Comparison of heart and coronary artery doses associated with intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for distal esophageal cancer[J].Int J Radiat Oncol Biol Phys,2012,83(5):1580-1586.DOI:10.1016/j.ijrobp.2011.10.053. [23] Lin SH,Wang L,Myles B,et al. Propensity score-based comparison of long-term outcomes with 3-dimensional conformal radiotherapy vs. intensity-modulated radiotherapy for esophageal cancer[J].Int J Radiat Oncol Biol Phys,2012,84(5):1078-1085.DOI:10.1016/j.ijrobp.2012.02.015. [24] Freilich J,Hoffe SE,Almhanna K,et al. Comparative outcomes for three-dimensional conformal versus intensity-modulated radiationtherapy for esophageal cancer[J].Dis Esophagus,2015,28(4):352-357.DOI:10.1111/dote.12203. [25] Lin SH,Zhang N,GodbyJ,et al. Radiation modality use and cardiopulmonary mortality risk in elderly patients with esophageal cancer[J].Cancer,2016,122(6):917-928.DOI:10.1002/cncr.29857. [26] 谭立君,刘晓,肖泽芬,等.592例食管癌3DRT的预后分析[J].中华放射肿瘤学杂志,2015,24(1):10-15.DOI:10.3760/cma.j.issn.1004-4221.2015.01.004. Tan LJ,Liu X,Xiao ZF,et al. The prognostic analysis of 3DRT for 592 cases of esophageal carcinoma[J].Chin J Radiat Oncol,2015,24(1):10-15.DOI:10.3760/cma.j.issn.1004-4221.2015.01.004. [27] Uno T,Isobe K,Kawakami H,et al. Efficacy and toxicities of concurrent chemo radiation for elderly patients with esophageal cancer[J].Anticancer Res,2004,24(4):2483-2486. [28] Nallapareddy S,Wilding GE,Yang G,et al. Chemoradiation is a tolerable therapy for older adults with esophageal cancer[J].Anticancer Res,2005,25(4):3055-3060. [29] Anderson SE,Minsky BD,Bains M,et al. Combined modality chemoradiation in elderly oesophageal cancer patients[J].Br J Cancer,2007,96(12):1823-1287.DOI:10.1038/sj.bjc.6603821. [30] Tougeron D,Di Fiore F,Thureau S,et al. Safety and outcome of definitive chemoradiotherapy in elderly patients with oesophageal cancer[J].Br J Cancer,2008,99(10):1586-1592.DOI:10.1038/sj.bjc.6604749. [31] Wakui R,Yamashita H,Okuma K,et al. Esophageal cancer:definitive chemoradiotherapy for elderly patients[J].Dis Esophagus,2010,23(7):572-579.DOI:10.1111/j.1442-2050.2010.01062.x. [32] Zhang P,Xi M,Zhao L,et al. Is there a benefit in receiving concurrent chemoradiotherapy for elderly patients with inoperable thoracic esophageal squamous cell carcinoma?[J/OL].PLoS One,2014,9(8):e105270.DOI:10.1371/journal.pone.0105270. [33] Rochigneux P,Resbeut M,Rousseau F,et al. Radio (chemo) therapy in elderly patients with esophageal cancer:a feasible treatment with an outcome consistent with younger patients[J].Front Oncol,2014,4:100.DOI:10.3389/fonc.2014.00100. [34] Lu XX,Wu H,Wang JH,et al. Short-and long-term outcomes of definitive chemoradiotherapy in patients with esophageal carcinoma aged≥75 years[J]. Mol Clin Oncol,2014,2(2):297-301.DOI:10.3892/mco.2013.235. [35] 胡学军,王尚前,邵国安,等.替吉奥与氟尿嘧啶治疗中晚期消化道肿瘤疗效的系统评价[J].中国全科医学,2012,15(17):1965-1970.DOI:10.3969/j.issn.1007-9572.2012.06.060. Hu XJ,Wang SQ,Shao GA,et al. The systematic evaluation of the curative effect of triggio and fluorouracil in the treatment of advanced gastrointestinal tumors[J].Chin General Med,2012,15(17):1965-1970.DOI:10.3969/j.issn.1007-9572.2012.06.060. [36] 王向前,蔡晶,顾红芳,等.放疗同步联合替吉奥治疗老年食管癌的临床观察[J].临床肿瘤学杂志,2013,18(5):434-437.DOI:10.3969/j.issn.1009-0460.2013.05.012. Wang XQ,Cai J,Gu HF,et al. Clinical study on the treatment of aged esophageal cancer by radiotherapy syndigio[J].J Clin Oncol,2013,18(5):434-437.DOI:10.3969/j.issn.1009-0460.2013.05.012. [37] 李向阳,卜祥兆,周冲,等.三维适形放射治疗联合替吉奥治疗老年食管癌的临床观察[J].现代肿瘤医学,2013,21(10):2263-2265.DOI:10.3969/j.issn.1672-4992.2013.10.38. Li XY,Bo XZ,Zhou C,et al. Clinical observation on the treatment of aged esophageal cancer by using three-dimensional conformal radiotherapy combined with teggio[J].Mod Oncol Med,2013,21(10):2263-2265.DOI:10.3969/j.issn.1672-4992.2013.10.38. [38] 王光明.替吉奥联合三维适形同期放疗治疗老年食管癌的临床观察[J].安徽医学,2013,34(7):920-922.DOI:10.3969/j.issn.1000-0399.2013.07.021. Wang GM.Clinical observation on the treatment of aged esophageal cancer in giogio and 3 d conformal radiotherapy in the same period[J].Anhui Med,2013,34(7):920-922.DOI:10.3969/j.issn.1000-0399.2013.07.021. [39] 陈大朝,庄建发,魏天安.调强放疗联合替吉奥治疗未手术老年食管癌的近期疗效[J].实用癌症杂志,2014,29(8):963-965.DOI:10.3969/j.issn.1001-5930.2014.08.024. Chen DC,ZHuang JF,Wei TA.The recent curative effect of combined radiotherapy combined with tigio for untreated elderly esophageal cancer[J]. J Appl Cancer,2014,29(8):963-965.DOI:10.3969/j.issn.1001-5930.2014.08.024. [40] Ji YL,Qiu GQ,Sheng LM,et al. A phase I dose escalation study of S-1 with concurrent radiotherapy in elderly patients with esophageal cancer[J].J Thorac Dis,2016,8(3):451-458.DOI:10.21037/jtd.2016.02.70. [41] Lyu SL,Fang M,Yang J,et al. Long-term results of definitive concurrent chemoradiotherapy using S-1 in the treatment of geriatric patients with esophageal cancer[J].Onco Targets Ther,2016,9:5389-5397.DOI:10.2147/OTT.S107668. [42] Song GM,Tian X,Liu XL,et al. Concurrent chemo-radiotherapy with S-1 as an alternative therapy for elderly Chinese patients with non-metastatic esophageal squamous cancer:evidence based on a systematic review and meta-analysis[J].Oncotarget,2017,8(23):37963-37973.DOI:10.18632/oncotarget.16302. [43] Popa EC,Shah MA.Capecitabine in the treatment of esophageal and gastric cancers[J].Expert Opin Investig Drugs,2013,22(12):1645-1657.DOI:10.1517/13543784.2013.842974. [44] 陈敬生,孟平,乔小燕,等.卡培他滨联合三维适形放疗治疗老年中晚期食管癌的临床疗效观察[J].肿瘤药学,2013,3(2):126-129.DOI:10.3969/j.issn.2095-1264.2013.030. Chen JS,Meng P,Qiao XY,et al. The clinical effect of capecitabine combined 3 d conformal radiotherapy in treatment of advanced esophageal cancer in elderly patients[J].Tumor Pharmacol,2013,3(2):126-129.DOI:10.3969/j.issn.2095-1264.2013.030 [45] 胡水清,朱卫国,甘雅娴,等.放疗联合希罗达和单纯放疗对老年食管癌生活质量的影响[J].现代肿瘤医学,2013,21(3):563-565.DOI:10.3969/j.issn.1672-4992.2013.03.36. Hu GQ,Zhu WG,Gan YX,et al. Effects of radiotherapy combined with hiroda and simple radiotherapy on the quality of life of aged esophageal cancer[J]. Mod Oncol Med,2013,21(3):563-565.DOI:10.3969/j.issn.1672-4992.2013.03.36. [46] 张欣平,李光明,郭翠华,等.放疗联合卡培他滨治疗老年食管癌[J].西部医学,2014,26(7):865-868.DOI:10.3969/j.issn.1672-3511.2014.07.016. Zhang XP,Li GM,Guo CH,et al. Radiotherapy combined with capecitabine for the treatment of aged esophageal cancer[J].Western Med,2014,26(7):865-868.DOI:10.3969/j.issn.1672-3511.2014.07.016. [47] 王晓阳,刘建华,郑广进.卡培他滨联合三维适形放疗治疗老年中晚期食管癌的疗效观察[J].现代诊断与治疗,2014,25(1):63-64. Wangle XY,Liu JH,Zheng GJ.The curative effect of capecitabine combined with three-dimensional radiotherapy for the treatment of advanced esophageal cancer in elderly patients[J].Mod Diag Treat,2014,25(1):63-64. [48] 王全玉,何炜.调强放疗联合卡培他滨单药治疗老年中晚期食管癌的临床研究[J].现代消化及介入诊疗,2015,20(3):268-270.DOI:10.3969/j.issn.1672-2159.2015.03.033. Wangle QY,He W.The clinical study on the treatment of advanced esophageal cancer in elderly patients with combined radiotherapy combined with radiotherapy combined with capecitabine[J].Mod Digest Intervent Ther,2015,20(3):268-270.DOI:10.3969/j.issn.1672-2159.2015.03.033. [49] 刘佳.调强放疗联合卡培他滨治疗老年中晚期食管癌的近期临床疗效[J].临床研究,2016,24(9):70-71. Liu J.The recent clinical effect of combined radiotherapy combined with capecitabine in the treatment of advanced esophageal cancer in elderly patients[J]. Clin Study,2016,24(9):70-71 [50] 李路路,陈剑,张鼎儒,等.卡培他滨同步放疗治疗食管癌的Meta分析[J].中国实用医刊,2016,43(16):12-16.DOI:10.3760/cma.j.issn.1674-4756.2016.16.005. Li LL,Chen J,Zhang DR,et al. A meta-analysis of the treatment of esophageal cancer by capecitabine radiotherapy[J].Chin J Pract Med,2016,43(16):12-16.DOI:10.3760/cma.j.issn.1674-4756.2016.16.005. [51] Safran H,Dipetrillo T,Akerman P,et al. Phase Ⅰ/Ⅱ study of trastuzumab,paclitaxel,cisplatin and radiation for locally advanced,HER2 overexpressing,esophageal adenocarcinoma[J].Int J Radiat Oncol Biol Phys,2007,67(2):405-409.DOI:10.1016/j.ijrobp.2006.08.076. [52] Dawson SJ,Michael M,Biagi J,et al. A phase Ⅰ/Ⅱ trial of celecoxib with chemotherapy and radiotherapy in the treatment of patients with locally advanced oesophageal cancer[J].Invest New Drugs,2007,25(2):123-129.DOI:10.1007/s10637-006-9016-5. [53] Safran H,Suntharalingam M,Dipetrillo T,et al. Cetuximab with concurrent chemoradiation for esophagogastric cancer:assessment of toxicity[J].Int J Radiat Oncol Biol Phys,2008,70(2):391-395.DOI:10.1016/j.ijrobp.2007.07.2325. [54] Javle M,Pande A,Iyer R,et al. Pilot study of gefitinib,oxaliplatin,and radiotherapy for esophageal adenocarcinoma:tissue effect predicts clinical response[J].Am J Clin Oncol,2008,31(4):329-334.DOI:10.1097/COC.0b013e318161 dc04. [55] Li G,Hu W,Wang JH,et al. Phase Ⅱ study of concurrent chemoradiation in combination with erlotinib for locally advanced esophageal carcinoma[J].Int J Radiat Oncol Biol Phys,2010,78(5):1407-1412.DOI:10.1016/j.ijrobp.2009.10.012. [56] Zhao KL,Hu XC,Wu XH,et al. A phase I dose escalation study of Nimotuzumab in combination with concurrent chemoradiation for patients with locally advanced squamous cell carcinoma of esophagus[J].Invest New Drugs,2012,30(4):1585-1590.DOI:10.1007/s10637-011-9735-0. [57] Liang J,E MY,Wu G,et al. Nimotuzumab combined with radiotherapy for esophageal cancer:preliminary study of a Phase Ⅱ clinical trial[J].Onco Targets Ther,2013,6:1589-1596.DOI:10.2147/OTT.S50945. [58] Iyer R,Chhatrala R,Shefter T,et al. Erlotinib and radiation therapy for elderly patients with esophageal cancer – clinical and correlative results from a prospective multicenter phase 2 trial[J].Oncology,2013,85(1):53-58.DOI:10.1159/000351617. [59] Zhai Y,Hui Z,Wang J,et al. Concurrent erlotinib and radiotherapy for chemoradiotherapy-intolerant esophageal squamous cell carcinoma patients:results of a pilot study[J].Dis Esophagus,2013,26(5):503-509.DOI:10.1111/j.1442-2050.2012.01380.x. [60] Crosby T,Hurt CN,Falk S,et al. Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1):amulticentre,phase 2/3 randomised trial[J].Lancet Oncol,2013,14(7):627-637.DOI:10.1016/S1470-2045(13)70136-0. [61] Ramos-Suzarte M,Lorenzo-Luaces P,Lazo NG,et al. Treatment of malignant,non-resectable,epithelial origin esophageal tumours with the humanized anti-epidermal growth factor antibody nimotuzumab combined with radiationtherapy and chemotherapy[J].Cancer Biol Ther,2012,13(8):600-605.DOI:10.4161/cbt.19849. [62] Yoshimoto Y,Kono K,Suzuki Y.Anti-tumor immune responses induced by radiotherapy:a review[J].Fukushima J Med Sci,2015,61(1):13-22.DOI:10.5387/fms.2015-6. [63] Apetoh L,Ghiringhelli F,Tesniere A,et al. Toll-like receptor 4-dependent contribution of the immune system to anticancer chemotherapy and radiotherapy[J].Nat Med,2007,13(9):1050-1059.DOI:10.1038/nm1622. [64] Apetoh L,Ghiringhelli F,Tesniere A,et al. The interaction between HMGB1 and TLR4 dictates the outcome of anticancer chemotherapy and radiotherapy[J].Immunol Rev,2007,220(1):47-59.DOI:10.1111/j.1600-065X.2007.00573.x. [65] Siva S,Macmanus MP,Martin RF,et al. Abscopal effects of radiation therapy:a clinical review for the radiobiologist[J].Cancer Lett,2015,356(1):82-90.DOI:10.1016/j.canlet.2013.09.018. [66] Kono K,Mimura K,Kiessling R.Immunogenic tumor cell death induced by chemoradiotherapy:molecular mechanisms and a clinicaltranslation[J].Cell Death Dis,2013,4(6):e688.DOI:10.1038/cddis.2013.207. [67] Yan L,Wu M,Ba N,et al. Efficacy of dendritic cell-cytokine-induced killer immunotherapy plus intensity-modulatedradiationtherapy intreating elderly patients with esophageal carcinoma[J].Genet Mol Res,2015,14(1):898-905.DOI:10.4238/2015.February.2.13. [68] An efficacy study in gastric and gastroesophageal junction cancer comparing ipilimumab versus standard of care immediately following first line chemotherapy[EB/OL].(2012-04-25).https://clinicaltrials.gov/ct2/show/NCT01585987. [69] Ohigashi Y,Sho M,Yamada Y,et al. Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand-2 expressionin human esophageal cancer[J].Clin Cancer Res,2005,11(8):2947-2953.DOI:10.1158/1078-0432.CCR-04-1469. [70] Le DT.Safety and activity of nivolumabmonotherapy in advanced and metastatic (A/M) gastric or gastroesophageal junction cancer (GC/GEC):results from the CheckMate-032 study[C]//Proceedings of Abstract Meeting ASCO GI 2015.San Fransisco,CA,USA:2015. [71] Study of pembrolizumab (mk-3475) in previously-treated participants with advanced carcinoma of the esophagus or esophagogastric junction (MK-3475-180/KEYNOTE-180)[EB/OL].(2015-09-23).https://clinicaltrials.gov/ct2/show/NCT02559687. [72] Zhang WC,Pang QS,Zhang XD,et al. Programmed death-ligand 1 is prognostic factor in esophageal squamous cell carcinoma and is associated with epidermal growth factor receptor[J].Cancer Sci,2017,108(4):590-597.DOI:10.1111/cas.13197.