食管鳞癌新辅助治疗现状与争议
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摘要
手术是治疗可切除食管鳞癌的首选治疗方案,然而对于局部进展期患者,食管癌的治疗更多强调多学科综合治疗,但目前食管癌的最佳综合治疗策略尚无统一标准。近年来,新辅助治疗在临床上受到学者的广泛关注,但仍存在诸多争议,包括新辅助治疗方案的选择、新辅助治疗后手术时机的选择、新辅助治疗后术后辅助治疗的选择、新辅助与辅助治疗的选择以及新辅助治疗敏感性检测等。本文就目前食管鳞癌新辅助治疗的现状和存在的争议做一综述。
Surgery is the first choice of treatment for resectable esophageal squamous cell carcinoma. However, for locally advanced patients, the treatment of esophageal cancer requires a more multidisciplinary, comprehensive approach. Nevertheless, there is no unified standard that defines the best comprehensive treatment strategy for esophageal cancer. In recent years, neoadjuvant therapy has been widely considered as the best treatment by practitioners, but there are still many controversies, including those related to the selection of a neoadjuvant therapy scheme, timing of surgery after neoadjuvant therapy, choice of postoperative adjuvant therapy after neoadjuvant therapy, choice of neoadjuvant and adjuvant therapy, and sensitivity testing of neoadjuvant therapy. In this paper,the present situation and controversies regarding the application of neoadjuvant therapy for esophageal squamous cell carcinoma are reviewed systematically.
Surgery is the first choice of treatment for resectable esophageal squamous cell carcinoma. However, for locally advanced patients, the treatment of esophageal cancer requires a more multidisciplinary, comprehensive approach. Nevertheless, there is no unified standard that defines the best comprehensive treatment strategy for esophageal cancer. In recent years, neoadjuvant therapy has been widely considered as the best treatment by practitioners, but there are still many controversies, including those related to the selection of a neoadjuvant therapy scheme, timing of surgery after neoadjuvant therapy, choice of postoperative adjuvant therapy after neoadjuvant therapy, choice of neoadjuvant and adjuvant therapy, and sensitivity testing of neoadjuvant therapy. In this paper,the present situation and controversies regarding the application of neoadjuvant therapy for esophageal squamous cell carcinoma are reviewed systematically.
引文
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[2]张思维,郑荣寿,左婷婷,等.中国食管癌死亡状况和生存分析[J].中华肿瘤杂志,2016,38(9):709-715.
[3]何炜,樊青霞.局部晚期食管癌的围手术期治疗策略[J].中国肿瘤临床,2016,43(12):511-515.
[4]Kelsen DP,Winter KA,Gunderson LL,et al.Long-term results of RTOGtrial 8911(USA Intergroup 113):a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer[J].J Clin Oncol,2007,25(24):3719-3725.
[5]Allum WH,Stenning SP,Bancewicz J,et al.Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer[J].J Clin Oncol,2009,27(30):5062-5067.
[6]Ychou M,Boige V,Pignon JP,et al.Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma:an FNCLCC and FFCD multicenter phaseⅢtrial[J].J Clin Oncol,2011,29(13):1715-1721.
[7]Ando N,Kato H,Igaki H,et al.A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus(JCOG9907)[J].Ann Surg Oncol,2012,19(1):68-74.
[8]Chan K,Saluja R,Delos SK,et al.Neoadjuvant treatments for locally advanced,resectable esophageal cancer:A network meta-analysis[J].Int J Cancer,2018,143(2):430-437.
[9]Boonstra JJ,Kok TC,Wijnhoven BP,et al.Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma:long-term results of a randomized controlled trial[J].BMC Cancer,2011,(11):181.
[10]Hara H,Tahara M,Daiko H,et al.PhaseⅡfeasibility study of preoperative chemotherapy with docetaxel,cisplatin,and fluorouracil for esophageal squamous cell carcinoma[J].Cancer Sci,2013,104(11):1455-1460.
[11]Zheng Y,Li Y,Liu X,et al.A phaseⅢ,multicenter randomized controlled trial of neo-adjuvant chemotherapy paclitaxel plus cisplatin versus surgery alone for stageⅡA-ⅢB esophageal squamous cell carcinoma[J].J Thorac Dis,2017,9(1):200-204.
[12]闫海霞,符国胜.术前放疗对食管癌患者影响的临床分析[J].当代医学,2011,17(16):21-22.
[13]van Hagen P,Hulshof MC,van Lanschot JJ,et al.Preoperative chemoradiotherapy for esophageal or junctional cancer[J].N Engl JMed,2012,366(22):2074-2084.
[14]Oppedijk V,van der Gaast A,van Lanschot JJ,et al.Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials[J].J Clin Oncol,2014,32(5):385-391.
[15]Tepper J,Krasna MJ,Niedzwiecki D,et al.PhaseⅢtrial of trimodality therapy with cisplatin,fluorouracil,radiotherapy,and surgery compared with surgery alone for esophageal cancer:CALGB 9781[J].J Clin Oncol,2008,26(7):1086-1092.
[16]Yang H,Liu H,Chen Y,et al.Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus(NEOCRTEC5010):A phaseⅢmulticenter,randomized,open-label clinical trial[J].J Clin Oncol,2018,36(27):2796-2803.
[17]Haisley KR,Hart KD,Nabavizadeh N,et al.Neoadjuvant chemoradiotherapy with concurrent cisplatin/5-fluorouracil is associated with increased pathologic complete response and improved survival compared to carboplatin/paclitaxel in patients with locally advanced esophageal cancer[J].Dis Esophagus,2017,30(7):1-7.
[18]Ai D,Chen Y,Liu Q,et al.Comparison of paclitaxel in combination with cisplatin(TP),carboplatin(TC)or fluorouracil(TF)concurrent with radiotherapy for patients with local advanced oesophageal squamous cell carcinoma:a three-arm phaseⅢrandomized trial(ESO-Shanghai2)[J].BMJ Open,2018,8(10):e20785.
[19]Mariette C,Dahan L,Mornex F,et al.Surgery alone versus chemoradiotherapy followed by surgery for stageⅠandⅡesophageal cancer:final analysis of randomized controlled phaseⅢtrial FFCD 9901[J].JClin Oncol,2014,32(23):2416-2422.
[20]Hamai Y,Hihara J,Taomoto J,et al.Effects of neoadjuvant chemoradiotherapy on postoperative morbidity and mortality associated with esophageal cancer[J].Dis Esophagus,2015,28(4):358-364.
[21]郭晓彤,赫捷.食管癌治疗现状及精准医学时代展望[J].中华肿瘤杂志,2016,38(9):641-645.
[22]Stahl M,Walz MK,Stuschke M,et al.PhaseⅢcomparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction[J].J Clin Oncol,2009,27(6):851-856.
[23]Klevebro F,Alexandersson DG,Wang N,et al.A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction[J].Ann Oncol,2016,27(4):660-667.
[24]Li F,Ding N,Zhao Y,et al.The current optimal multimodality treatments for oesophageal squamous-cell carcinoma:A systematic review and meta-analysis[J].Int J Surg,2018,(60):88-100.
[25]Stiles BM,Kamel MK,Harrison SW,et al.Neoadjuvant Therapy for Locally Advanced Esophageal Cancer Should Be Targeted to Tumor Histology[J].Ann Thorac Surg,2019,107(1):187-193.
[26]唐鹏,段晓峰,姜宏景,等.1例中晚期食管癌新辅助放化疗联合微创手术治疗探讨[J].中国肿瘤临床,2014,41(6):399-403.
[27]Tang H,Tan L,Shen Y,et al.CMISG1701:a multicenter prospective randomized phaseⅢclinical trial comparing neoadjuvant chemoradiotherapy to neoadjuvant chemotherapy followed by minimally invasive esophagectomy in patients with locally advanced resectable esophageal squamous cell carcinoma(c T3-4a N0-1M0)(NCT03001596)[J].BMC Cancer,2017,17(1):450.
[28]Miyazaki T,Ojima H,Fukuchi M,et al.PhaseⅡStudy of Docetaxel,Nedaplatin,and 5-Fluorouracil Combined Chemotherapy for Advanced Esophageal Cancer[J].Ann Surg Oncol,2015,22(11):3653-3658.
[29]Sato M,Ando N.Neoadjuvant chemotherapy followed by surgery as standard treatment for stageⅡ+Ⅲthoracic esophageal squamous cell carcinoma in Japan[J].Nihon Geka Gakkai Zasshi,2011,112(2):104-110.
[30]Zou B,Pang J,Liu Y,et al.Postoperative chemoradiotherapy improves survival in patients with stageⅡ-Ⅲesophageal squamous cell carcinoma:An analysis of clinical outcomes[J].Thorac Cancer,2016,7(5):515-521.
[31]Hsu PK,Chen HS,Liu CC,et al.Pre-versus postoperative chemoradiotherapy for locally advanced esophageal squamous cell carcinoma[J].J Thorac Cardiovasc Surg,2017,154(2):732-740.
[32]Hsu PK,Chen HS,Liu CC,et al.Neoadjuvant chemoradiation versus upfront esophagectomy in clinical stageⅡandⅢesophageal squamous cell carcinoma[J].Ann Surg Oncol,2019,26(2):506-513.
[33]Kathiravetpillai N,Koeter M,van der Sangen MJ,et al.Delaying surgery after neoadjuvant chemoradiotherapy does not significantly influence postoperative morbidity or oncological outcome in patients with oesophageal adenocarcinoma[J].Eur J Surg Oncol,2016,42(8):1183-1190.
[34]Chiu CH,Chao YK,Chang HK,et al.Interval between neoadjuvant chemoradiotherapy and surgery for esophageal squamous cell carcinoma:does delayed surgery impact outcome[J]?Ann Surg Oncol,2013,20(13):4245-4251.
[35]Wang BY,Chen HS,Hsu PK,et al.Clinical impact of the interval between chemoradiotherapy and esophagectomy in esophageal squamous cell carcinoma patients[J].Ann Thorac Surg,2015,99(3):947-955.
[36]Lin G,Han SY,Xu YP,et al.Increasing the interval between neoadjuvant chemoradiotherapy and surgery in esophageal cancer:a meta-analysis of published studies[J].Dis Esophagus,2016,29(8):1107-1114.
[37]Hsu HY,Chao YK,Hsieh CH,et al.Postoperative adjuvant therapy improves survival in pathologic nonresponders after neoadjuvant chemoradiation for esophageal squamous cell carcinoma:A propensity-matched analysis[J].Ann Thorac Surg,2016,102(5):1687-1693.
[38]Kim GJ,Koshy M,Hanlon AL,et al.The benefit of chemotherapy in esophageal cancer patients with residual disease after trimodality therapy[J].Am J Clin Oncol,2016,39(2):136-141.
[39]Brescia AA,Broderick SR,Crabtree TD,et al.Adjuvant therapy for positive nodes after induction therapy and resection of esophageal cancer[J].Ann Thorac Surg,2016,101(1):200-208.
[40]Hamai Y,Emi M,Ibuki Y,et al.Early recurrence and cancer death after trimodal therapy for esophageal squamous cell carcinoma[J].Anticancer Res,2019,39(3):1433-1440.
[41]Jeong Y,Kim JH,Kim SB,et al.Role of surgical resection in complete responders on FDG-PET after chemoradiotherapy for locally advanced esophageal squamous cell carcinoma[J].J Surg Oncol,2014,109(5):472-477.
[42]Castoro C,Scarpa M,Cagol M,et al.Complete clinical response after neoadjuvant chemoradiotherapy for squamous cell cancer of the thoracic oesophagus:is surgery always necessary[J]?J Gastrointest Surg,2013,17(8):1375-1381.
[43]Wang J,Qin J,Jing S,et al.Clinical complete response after chemoradiotherapy for carcinoma of thoracic esophagus:Is esophagectomy always necessary?A systematic review and meta-analysis[J].Thorac Cancer,2018,9(12):1638-1647.
[44]Miyata H,Yamasaki M,Takahashi T,et al.Determinants of response to neoadjuvant chemotherapy for esophageal cancer using 18F-fluorodeoxiglucose positron emission tomography(18F-FDG-PET)[J].Ann Surg Oncol,2014,21(2):575-582.
[45]Goense L,Ruurda JP,Carter BW,et al.Prediction and diagnosis of interval metastasis after neoadjuvant chemoradiotherapy for oesophageal cancer using(18)F-FDG PET/CT[J].Eur J Nucl Med Mol Imaging,2018,45(10):1742-1751.
[46]Burtness B,Ilson D,Iqbal S.New directions in perioperative management of locally advanced esophagogastric cancer[J].Am Soc Clin Oncol Educ Book,2014:e172-e178.
[2]张思维,郑荣寿,左婷婷,等.中国食管癌死亡状况和生存分析[J].中华肿瘤杂志,2016,38(9):709-715.
[3]何炜,樊青霞.局部晚期食管癌的围手术期治疗策略[J].中国肿瘤临床,2016,43(12):511-515.
[4]Kelsen DP,Winter KA,Gunderson LL,et al.Long-term results of RTOGtrial 8911(USA Intergroup 113):a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer[J].J Clin Oncol,2007,25(24):3719-3725.
[5]Allum WH,Stenning SP,Bancewicz J,et al.Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer[J].J Clin Oncol,2009,27(30):5062-5067.
[6]Ychou M,Boige V,Pignon JP,et al.Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma:an FNCLCC and FFCD multicenter phaseⅢtrial[J].J Clin Oncol,2011,29(13):1715-1721.
[7]Ando N,Kato H,Igaki H,et al.A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus(JCOG9907)[J].Ann Surg Oncol,2012,19(1):68-74.
[8]Chan K,Saluja R,Delos SK,et al.Neoadjuvant treatments for locally advanced,resectable esophageal cancer:A network meta-analysis[J].Int J Cancer,2018,143(2):430-437.
[9]Boonstra JJ,Kok TC,Wijnhoven BP,et al.Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma:long-term results of a randomized controlled trial[J].BMC Cancer,2011,(11):181.
[10]Hara H,Tahara M,Daiko H,et al.PhaseⅡfeasibility study of preoperative chemotherapy with docetaxel,cisplatin,and fluorouracil for esophageal squamous cell carcinoma[J].Cancer Sci,2013,104(11):1455-1460.
[11]Zheng Y,Li Y,Liu X,et al.A phaseⅢ,multicenter randomized controlled trial of neo-adjuvant chemotherapy paclitaxel plus cisplatin versus surgery alone for stageⅡA-ⅢB esophageal squamous cell carcinoma[J].J Thorac Dis,2017,9(1):200-204.
[12]闫海霞,符国胜.术前放疗对食管癌患者影响的临床分析[J].当代医学,2011,17(16):21-22.
[13]van Hagen P,Hulshof MC,van Lanschot JJ,et al.Preoperative chemoradiotherapy for esophageal or junctional cancer[J].N Engl JMed,2012,366(22):2074-2084.
[14]Oppedijk V,van der Gaast A,van Lanschot JJ,et al.Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials[J].J Clin Oncol,2014,32(5):385-391.
[15]Tepper J,Krasna MJ,Niedzwiecki D,et al.PhaseⅢtrial of trimodality therapy with cisplatin,fluorouracil,radiotherapy,and surgery compared with surgery alone for esophageal cancer:CALGB 9781[J].J Clin Oncol,2008,26(7):1086-1092.
[16]Yang H,Liu H,Chen Y,et al.Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone for locally advanced squamous cell carcinoma of the esophagus(NEOCRTEC5010):A phaseⅢmulticenter,randomized,open-label clinical trial[J].J Clin Oncol,2018,36(27):2796-2803.
[17]Haisley KR,Hart KD,Nabavizadeh N,et al.Neoadjuvant chemoradiotherapy with concurrent cisplatin/5-fluorouracil is associated with increased pathologic complete response and improved survival compared to carboplatin/paclitaxel in patients with locally advanced esophageal cancer[J].Dis Esophagus,2017,30(7):1-7.
[18]Ai D,Chen Y,Liu Q,et al.Comparison of paclitaxel in combination with cisplatin(TP),carboplatin(TC)or fluorouracil(TF)concurrent with radiotherapy for patients with local advanced oesophageal squamous cell carcinoma:a three-arm phaseⅢrandomized trial(ESO-Shanghai2)[J].BMJ Open,2018,8(10):e20785.
[19]Mariette C,Dahan L,Mornex F,et al.Surgery alone versus chemoradiotherapy followed by surgery for stageⅠandⅡesophageal cancer:final analysis of randomized controlled phaseⅢtrial FFCD 9901[J].JClin Oncol,2014,32(23):2416-2422.
[20]Hamai Y,Hihara J,Taomoto J,et al.Effects of neoadjuvant chemoradiotherapy on postoperative morbidity and mortality associated with esophageal cancer[J].Dis Esophagus,2015,28(4):358-364.
[21]郭晓彤,赫捷.食管癌治疗现状及精准医学时代展望[J].中华肿瘤杂志,2016,38(9):641-645.
[22]Stahl M,Walz MK,Stuschke M,et al.PhaseⅢcomparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction[J].J Clin Oncol,2009,27(6):851-856.
[23]Klevebro F,Alexandersson DG,Wang N,et al.A randomized clinical trial of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for cancer of the oesophagus or gastro-oesophageal junction[J].Ann Oncol,2016,27(4):660-667.
[24]Li F,Ding N,Zhao Y,et al.The current optimal multimodality treatments for oesophageal squamous-cell carcinoma:A systematic review and meta-analysis[J].Int J Surg,2018,(60):88-100.
[25]Stiles BM,Kamel MK,Harrison SW,et al.Neoadjuvant Therapy for Locally Advanced Esophageal Cancer Should Be Targeted to Tumor Histology[J].Ann Thorac Surg,2019,107(1):187-193.
[26]唐鹏,段晓峰,姜宏景,等.1例中晚期食管癌新辅助放化疗联合微创手术治疗探讨[J].中国肿瘤临床,2014,41(6):399-403.
[27]Tang H,Tan L,Shen Y,et al.CMISG1701:a multicenter prospective randomized phaseⅢclinical trial comparing neoadjuvant chemoradiotherapy to neoadjuvant chemotherapy followed by minimally invasive esophagectomy in patients with locally advanced resectable esophageal squamous cell carcinoma(c T3-4a N0-1M0)(NCT03001596)[J].BMC Cancer,2017,17(1):450.
[28]Miyazaki T,Ojima H,Fukuchi M,et al.PhaseⅡStudy of Docetaxel,Nedaplatin,and 5-Fluorouracil Combined Chemotherapy for Advanced Esophageal Cancer[J].Ann Surg Oncol,2015,22(11):3653-3658.
[29]Sato M,Ando N.Neoadjuvant chemotherapy followed by surgery as standard treatment for stageⅡ+Ⅲthoracic esophageal squamous cell carcinoma in Japan[J].Nihon Geka Gakkai Zasshi,2011,112(2):104-110.
[30]Zou B,Pang J,Liu Y,et al.Postoperative chemoradiotherapy improves survival in patients with stageⅡ-Ⅲesophageal squamous cell carcinoma:An analysis of clinical outcomes[J].Thorac Cancer,2016,7(5):515-521.
[31]Hsu PK,Chen HS,Liu CC,et al.Pre-versus postoperative chemoradiotherapy for locally advanced esophageal squamous cell carcinoma[J].J Thorac Cardiovasc Surg,2017,154(2):732-740.
[32]Hsu PK,Chen HS,Liu CC,et al.Neoadjuvant chemoradiation versus upfront esophagectomy in clinical stageⅡandⅢesophageal squamous cell carcinoma[J].Ann Surg Oncol,2019,26(2):506-513.
[33]Kathiravetpillai N,Koeter M,van der Sangen MJ,et al.Delaying surgery after neoadjuvant chemoradiotherapy does not significantly influence postoperative morbidity or oncological outcome in patients with oesophageal adenocarcinoma[J].Eur J Surg Oncol,2016,42(8):1183-1190.
[34]Chiu CH,Chao YK,Chang HK,et al.Interval between neoadjuvant chemoradiotherapy and surgery for esophageal squamous cell carcinoma:does delayed surgery impact outcome[J]?Ann Surg Oncol,2013,20(13):4245-4251.
[35]Wang BY,Chen HS,Hsu PK,et al.Clinical impact of the interval between chemoradiotherapy and esophagectomy in esophageal squamous cell carcinoma patients[J].Ann Thorac Surg,2015,99(3):947-955.
[36]Lin G,Han SY,Xu YP,et al.Increasing the interval between neoadjuvant chemoradiotherapy and surgery in esophageal cancer:a meta-analysis of published studies[J].Dis Esophagus,2016,29(8):1107-1114.
[37]Hsu HY,Chao YK,Hsieh CH,et al.Postoperative adjuvant therapy improves survival in pathologic nonresponders after neoadjuvant chemoradiation for esophageal squamous cell carcinoma:A propensity-matched analysis[J].Ann Thorac Surg,2016,102(5):1687-1693.
[38]Kim GJ,Koshy M,Hanlon AL,et al.The benefit of chemotherapy in esophageal cancer patients with residual disease after trimodality therapy[J].Am J Clin Oncol,2016,39(2):136-141.
[39]Brescia AA,Broderick SR,Crabtree TD,et al.Adjuvant therapy for positive nodes after induction therapy and resection of esophageal cancer[J].Ann Thorac Surg,2016,101(1):200-208.
[40]Hamai Y,Emi M,Ibuki Y,et al.Early recurrence and cancer death after trimodal therapy for esophageal squamous cell carcinoma[J].Anticancer Res,2019,39(3):1433-1440.
[41]Jeong Y,Kim JH,Kim SB,et al.Role of surgical resection in complete responders on FDG-PET after chemoradiotherapy for locally advanced esophageal squamous cell carcinoma[J].J Surg Oncol,2014,109(5):472-477.
[42]Castoro C,Scarpa M,Cagol M,et al.Complete clinical response after neoadjuvant chemoradiotherapy for squamous cell cancer of the thoracic oesophagus:is surgery always necessary[J]?J Gastrointest Surg,2013,17(8):1375-1381.
[43]Wang J,Qin J,Jing S,et al.Clinical complete response after chemoradiotherapy for carcinoma of thoracic esophagus:Is esophagectomy always necessary?A systematic review and meta-analysis[J].Thorac Cancer,2018,9(12):1638-1647.
[44]Miyata H,Yamasaki M,Takahashi T,et al.Determinants of response to neoadjuvant chemotherapy for esophageal cancer using 18F-fluorodeoxiglucose positron emission tomography(18F-FDG-PET)[J].Ann Surg Oncol,2014,21(2):575-582.
[45]Goense L,Ruurda JP,Carter BW,et al.Prediction and diagnosis of interval metastasis after neoadjuvant chemoradiotherapy for oesophageal cancer using(18)F-FDG PET/CT[J].Eur J Nucl Med Mol Imaging,2018,45(10):1742-1751.
[46]Burtness B,Ilson D,Iqbal S.New directions in perioperative management of locally advanced esophagogastric cancer[J].Am Soc Clin Oncol Educ Book,2014:e172-e178.