Review Article| Volume 32, ISSUE 1, P65-81, January 2023

The Perioperative and Operative Management of Esophageal and Gastric Cancer

Published:November 03, 2022DOI:


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribers receive full online access to your subscription and archive of back issues up to and including 2002.

      Content published before 2002 is available via pay-per-view purchase only.


      Subscribe to Surgical Oncology Clinics
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Sung H.
        • Ferlay J.
        • Siegel R.L.
        • et al.
        Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.
        CA Cancer J Clin. 2021; 71: 209-249
        • Machlowska J.
        • Baj J.
        • Sitarz M.
        • et al.
        Gastric Cancer : Epidemiology , Risk Factors , Classification , Genomic Characteristics and Treatment Strategies.
        Int J Mol Sci. 2020; 21: 4012
        • Iriarte F.
        • Su S.
        • Petrov R.v.
        • et al.
        Surgical Management of Early Esophageal Cancer.
        Surg Clin North Am. 2021; 101: 427-441
        • Leake P.A.
        • Cardoso R.
        • Seevaratnam R.
        • et al.
        A systematic review of the accuracy and indications for diagnostic laparoscopy prior to curative-intent resection of gastric cancer.
        Gastric Cancer. 2012; 15: 38-47
        • Alsop B.R.
        • Sharma P.
        Esophageal Cancer.
        Gastroenterol Clin North Am. 2016; 45: 399-412
        • He H.
        • Chen N.
        • Hou Y.
        • et al.
        Trends in the incidence and survival of patients with esophageal cancer: A SEER database analysis.
        Thorac Cancer. 2020; 11: 1121
        • Thrift A.P.
        • Nguyen T.H.
        Gastric Cancer Epidemiology.
        Gastrointest Endosc Clin North Am. 2021; 31: 425-439
        • Trivers K.F.
        • Sabatino S.A.
        • Stewart S.L.
        Trends in esophageal cancer incidence by histology, United States, 1998-2003.
        Int J Cancer. 2008; 123: 1422-1428
        • Avgerinos K.I.
        • Spyrou N.
        • Mantzoros C.S.
        • et al.
        Obesity and cancer risk: Emerging biological mechanisms and perspectives.
        Metab Clin Exp. 2019; 92: 121-135
        • Coleman H.G.
        • Xie S.H.
        • Lagergren J.
        The Epidemiology of Esophageal Adenocarcinoma.
        Gastroenterology. 2018; 154: 390-405
      1. Esophageal Cancer - American Family Physician.
        (Available at:) (Accessed April 2, 2022)
        • Karimi P.
        • Islami F.
        • Anandasabapathy S.
        • et al.
        Gastric Cancer: Descriptive Epidemiology, Risk Factors, Screening, and Prevention.
        Cancer Epidemiol Biomarkers Prev. 2014;
        • Rawla P.
        • Barsouk A.
        Epidemiology of gastric cancer: global trends, risk factors and prevention.
        Gastroenterol Rev. 2019; 14
        • Lauren P.
        The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma.
        Acta Pathol Microbiol Scand. 1965; 1: 31-49
        • Berlth F.
        • Bollschweiler E.
        • Drebber U.
        • et al.
        Pathohistological classification systems in gastric cancer: Diagnostic relevance and prognostic value.
        World J Gastroenterol. 2014; 20: 5679-5684
        • Rü Diger Siewert J.
        • Feith M.
        • Werner M.
        • et al.
        Adenocarcinoma of the Esophagogastric Junction Results of Surgical Therapy Based on Anatomical/Topographic Classification in 1,002 Consecutive Patients.
        Ann Surg. 2000; 232: 353-361
        • Shahbaz Sarwar C.M.
        • Luketich J.D.
        • Landreneau R.J.
        • et al.
        Esophageal cancer: An update.
        Int J Surg. 2010; 8: 417-422
        • di Pietro M.
        • Canto M.I.
        • Fitzgerald R.C.
        Endoscopic Management of Early Adenocarcinoma and Squamous Cell Carcinoma of the Esophagus: Screening, Diagnosis, and Therapy.
        Gastroenterology. 2018; 154: 421-436
        • Graham D.Y.
        • Schwartz J.T.
        • Cain G.D.
        • et al.
        Prospective evaluation of biopsy number in the diagnosis of esophageal and gastric carcinoma.
        Gastroenterology. 1982; 82: 228-231
      2. AJCC Cancer Staging Manual Eighth Edition.
        (Available at:) (Accessed April 20, 2022)
        • Rice T.W.
        • Ishwaran H.
        • Ferguson M.K.
        • et al.
        Cancer of the Esophagus and Esophagogastric Junction: An Eighth Edition Staging Primer.
        J Thorac Oncol. 2017; 12: 36-42
        • Betancourt-Cuellar S.L.
        • Benveniste M.F.K.
        • Palacio D.P.
        • et al.
        Esophageal Cancer: Tumor-Node-Metastasis Staging.
        Radiol Clin North Am. 2021; 59: 219-229
        • Krill T.
        • Baliss M.
        • Roark R.
        • et al.
        Accuracy of endoscopic ultrasound in esophageal cancer staging.
        J Thorac Dis. 2019; 11: S1602-S1609
        • Hong S.J.
        • Kim T.J.
        • Nam K.B.
        • et al.
        New TNM staging system for esophageal cancer: What chest radiologists need to know.
        Radiographics. 2014; 34: 1722-1740
        • Chen Z da
        • Zhang P.F.
        • Xi H.Q.
        • et al.
        Recent Advances in the Diagnosis, Staging, Treatment, and Prognosis of Advanced Gastric Cancer: A Literature Review.
        Front Med. 2021; 8: 744839
        • Van Zoonen M.
        • Van Oijen M.G.H.
        • Van Leeuwen M.S.
        • et al.
        Low impact of staging EUS for determining surgical resectability in esophageal cancer.
        Surg Endosc. 2012;
        • Shah P.M.
        • Gerdes H.
        Endoscopic options for early stage esophageal cancer.
        J Gastrointest Oncol. 2015; 6: 20-30
        • Spolverato G.
        • Ejaz A.
        • Kim Y.
        • et al.
        Use of endoscopic ultrasound in the preoperative staging of gastric cancer: a multi-institutional study of the US gastric cancer collaborative.
        J Am Coll Surg. 2015; 220: 48-56
        • Fairweather M.
        • Jajoo K.
        • Sainani N.
        • et al.
        Accuracy of EUS and CT imaging in preoperative gastric cancer staging.
        J Surg Oncol. 2015; 111: 1016-1020
        • Sarela A.I.
        • Lefkowitz R.
        • Brennan M.F.
        • et al.
        Selection of patients with gastric adenocarcinoma for laparoscopic staging.
        Am J Surg. 2006; 191: 134-138
        • American Joint Comission on Cancer
        AJCC Cancer Staging Manual.
        in: Amin M.B. Edge S.B. Greene F.L. AJCC cancer staging Manual. 8ht edition. Springer International Publishing, Chicago, IL2017: 185-202
        • Borggreve A.S.
        • Kingma B.F.
        • Domrachev S.A.
        • et al.
        Surgical treatment of esophageal cancer in the era of multimodality management.
        Ann N Y Acad Sci, 2018
        • Barreto J.C.
        • Posner M.C.
        Transhiatal versus transthoracic esophagectomy for esophageal cancer.
        World J Gastroenterol. 2010; 16: 3804
        • Omloo J.M.T.
        • Lagarde S.M.
        • Hulscher J.B.F.
        • et al.
        Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the mid/distal esophagus: five-year survival of a randomized clinical trial.
        Ann Surg. 2007; 246: 992-1000
        • Hulscher J.B.F.
        • van Sandick J.W.
        • de Boer A.G.E.M.
        • et al.
        Extended transthoracic resection compared with limited transhiatal resection for adenocarcinoma of the esophagus.
        N Engl J Med. 2002; 347: 1662-1669
        • Johansson J.
        • DeMeester T.R.
        • Hagen J.A.
        • et al.
        En bloc vs transhiatal esophagectomy for stage T3 N1 adenocarcinoma of the distal esophagus.
        Arch Surg. 2004; 139: 627-633
        • Takahashi C.
        • Shridhar R.
        • Huston J.
        • et al.
        Comparative outcomes of transthoracic versus transhiatal esophagectomy.
        Surgery. 2021; 170: 263-270
        • Wei M.T.
        • Zhang Y.C.
        • Deng X.B.
        • et al.
        Transthoracic vs transhiatal surgery for cancer of the esophagogastric junction: A meta-analysis META-ANALYSIS.
        World J Gastroenterol. 2014; 20: 10183-10192
        • Visser E.
        • Markar S.R.
        • Ruurda J.P.
        • et al.
        Prognostic Value of Lymph Node Yield on Overall Survival in Esophageal Cancer Patients: A Systematic Review and Meta-analysis.
        Ann Surg. 2019; 269: 261-268
        • Peyre C.G.
        • Hagen J.A.
        • DeMeester S.R.
        • et al.
        Predicting systemic disease in patients with esophageal cancer after esophagectomy a multinational study on the significance of the number of involved lymph nodes.
        Ann Surg. 2008; 248: 979-984
        • Schandl A.
        • Johar A.
        • Lagergren J.
        • et al.
        Lymphadenectomy and health-related quality of life after oesophageal cancer surgery: a nationwide, population-based cohort study.
        BMJ Open. 2016;
        • National Comprehensive Cancer Network
        Esophageal and Esophagogastric Junction Cancers (Version 2.2022).
        (Available at:) (Accessed May 9, 2022)
        • Johnston F.M.
        • Beckman M.
        Updates on Management of Gastric Cancer.
        Curr Oncol Rep. 2019; 21
        • National Comprehensive Cancer Network
        Gastric Cancer (Version 2.2022).
        (Available at:) (Accessed May 9, 2022)
        • Songun I.
        • Putter H.
        • Kranenbarg E.M.K.
        • et al.
        Surgical treatment of gastric cancer: 15-year follow-up results of the randomised nationwide Dutch D1D2 trial.
        Lancet Oncol. 2010; 11: 439-449
        • Degiuli M.
        • Reddavid R.
        • Tomatis M.
        • et al.
        D2 dissection improves disease-specific survival in advanced gastric cancer patients: 15-year follow-up results of the Italian Gastric Cancer Study Group D1 versus D2 randomised controlled trial.
        Eur J Cancer. 2021; 150: 10-22
        • Fujimura T.
        • Nakamura K.
        • Oyama K.
        • et al.
        Selective lymphadenectomy of para-aortic lymph nodes for advanced gastric cancer.
        Oncol Rep. 2009; 22: 509-514
        • Mocellin S.
        • Mcculloch P.
        • Kazi H.
        • et al.
        Extent of lymph node dissection for adenocarcinoma of the stomach.
        Cochrane Database Syst Rev. 2015; 2015
        • Biere S.S.A.Y.
        • van Berge Henegouwen M.I.
        • Maas K.W.
        • et al.
        Minimally invasive versus open oesophagectomy for patients with oesophageal cancer: a multicentre, open-label, randomised controlled trial.
        Lancet. 2012; 379: 1887-1892
        • Sgourakis G.
        • Gockel I.
        • Radtke A.
        • et al.
        Minimally invasive versus open esophagectomy: meta-analysis of outcomes.
        Dig Dis Sci. 2010; 55: 3031-3040
        • Smithers B.M.
        • Gotley D.C.
        • Martin I.
        • et al.
        Comparison of the Outcomes Between Open and Minimally Invasive Esophagectomy.
        Ann Surg. 2007; 245: 232
        • Sakamoto T.
        • Fujiogi M.
        • Matsui H.
        • et al.
        Comparing Perioperative Mortality and Morbidity of Minimally Invasive Esophagectomy Versus Open Esophagectomy for Esophageal Cancer: A Nationwide Retrospective Analysis.
        Ann Surg. 2021; 274: 324-330
        • Yibulayin W.
        • Abulizi S.
        • Lv H.
        • et al.
        Minimally invasive oesophagectomy versus open esophagectomy for resectable esophageal cancer: a meta-analysis.
        World J Surg Oncol. 2016; 14
        • Straatman J.
        • van der Wielen N.
        • Cuesta M.A.
        • et al.
        Minimally Invasive Versus Open Esophageal Resection: Three-year Follow-up of the Previously Reported Randomized Controlled Trial: the TIME Trial.
        Ann Surg. 2017; 266: 232-236
        • van der Sluis P.C.
        • van der Horst S.
        • May A.M.
        • et al.
        Robot-assisted Minimally Invasive Thoracolaparoscopic Esophagectomy Versus Open Transthoracic Esophagectomy for Resectable Esophageal Cancer: A Randomized Controlled Trial.
        Ann Surg. 2019; 269: 621-630
        • Yang Y.
        • Li B.
        • Yi J.
        • et al.
        Robot-assisted Versus Conventional Minimally Invasive Esophagectomy for Resectable Esophageal Squamous Cell Carcinoma: Early Results of a Multicenter Randomized Controlled Trial: The RAMIE Trial.
        Ann Surg. 2022; 275: 646-653
        • Huang C.
        • Liu H.
        • Hu Y.
        • et al.
        Laparoscopic vs Open Distal Gastrectomy for Locally Advanced Gastric Cancer: Five-Year Outcomes From the CLASS-01 Randomized Clinical Trial.
        JAMA Surg. 2022; 157: 9-17
        • Kim H.H.
        • Han S.U.
        • Kim M.C.
        • et al.
        Effect of Laparoscopic Distal Gastrectomy vs Open Distal Gastrectomy on Long-term Survival Among Patients With Stage I Gastric Cancer: The KLASS-01 Randomized Clinical Trial.
        JAMA Oncol. 2019; 5: 506-513
        • Huscher C.G.S.
        • Mingoli A.
        • Sgarzini G.
        • et al.
        Laparoscopic versus open subtotal gastrectomy for distal gastric cancer: five-year results of a randomized prospective trial.
        Ann Surg. 2005; 241: 232-237
        • Guerrini G.P.
        • Esposito G.
        • Magistri P.
        • et al.
        Robotic versus laparoscopic gastrectomy for gastric cancer: The largest meta-analysis.
        Int J Surg. 2020; 82: 210-228
        • Gong E.J.
        • Kim H.
        • Ahn J.Y.
        • et al.
        Comparison of long-term outcomes of endoscopic submucosal dissection and surgery for esophagogastric junction adenocarcinoma.
        Gastric Cancer. 2017;
        • Kim G.H.
        • Jung H.Y.
        Endoscopic Resection of Gastric Cancer.
        Gastrointest Endosc Clin North Am. 2021; 31: 563-579
        • Quero G.
        • Fiorillo C.
        • Longo F.
        • et al.
        Propensity score-matched comparison of short- and long-term outcomes between surgery and endoscopic submucosal dissection (ESD) for intestinal type early gastric cancer (EGC) of the middle and lower third of the stomach: a European tertiary referral center experience.
        Surg Endosc. 2021; 35: 2592-2600
        • Choi I.J.
        • Lee J.H.
        • Kim Y il
        • et al.
        Long-term outcome comparison of endoscopic resection and surgery in early gastric cancer meeting the absolute indication for endoscopic resection.
        Gastrointest Endosc. 2015; 81: 333-341.e1
        • Ahmed Y.
        • Othman M.
        EMR/ESD: Techniques, Complications, and Evidence.
        Curr Gastroenterol Rep. 2020;
        • Japanese Gastric Cancer Association
        Japanese gastric cancer treatment guidelines 2018 (5th edition) Preface to the English version.
        Gastric Cancer. 2021;
        • Pimentel-Nunes P.
        • Dinis-Ribeiro M.
        • Ponchon T.
        • et al.
        Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.
        Endoscopy. 2015; 47: 829-854
        • Wang J.
        • Zhang X.H.
        • Ge J.
        • et al.
        Endoscopic submucosal dissection vs endoscopic mucosal resection for colorectal tumors: A meta-analysis.
        World J Gastroenterol. 2014; 20: 8282-8287
        • Draganov P.v.
        • Wang A.Y.
        • Othman M.O.
        • et al.
        AGA Institute Clinical Practice Update: Endoscopic Submucosal Dissection in the United States.
        Clin Gastroenterol Hepatol. 2019; 17: 16-25.e1
        • Ishihara R.
        • Arima M.
        • Iizuka T.
        • et al.
        Endoscopic submucosal dissection/endoscopic mucosal resection guidelines for esophageal cancer.
        Dig Endosc. 2020;
        • Seshadri R.A.
        • Glehen O.
        Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer.
        World J Gastroenterol. 2016; 22: 1114
        • Wagner A.D.
        • Syn N.L.X.
        • Moehler M.
        • et al.
        Chemotherapy for advanced gastric cancer.
        Cochrane Database Syst Rev. 2017; 2017
        • Zhang J.F.
        • Lv L.
        • Zhao S.
        • et al.
        Hyperthermic Intraperitoneal Chemotherapy (HIPEC) Combined with Surgery: A 12-Year Meta-Analysis of this Promising Treatment Strategy for Advanced Gastric Cancer at Different Stages.
        Ann Surg Oncol. 2022; 29: 3170-3186
        • Bonnot P.E.
        • Piessen G.
        • Kepenekian V.
        • et al.
        Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Gastric Cancer With Peritoneal Metastases (CYTO-CHIP study): A Propensity Score Analysis.
        J Clin Oncol. 2019; 37: 2028-2040
        • Granieri S.
        • Bonomi A.
        • Frassini S.
        • et al.
        Prognostic impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) in gastric cancer patients: A meta-analysis of randomized controlled trials.
        Eur J Surg Oncol. 2021; 47: 2757-2767
        • Glehen O.
        • Passot G.
        • Villeneuve L.
        • et al.
        GASTRICHIP: D2 resection and hyperthermic intraperitoneal chemotherapy in locally advanced gastric carcinoma: a randomized and multicenter phase III study.
        BMC Cancer. 2014; 14
        • Koemans W.J.
        • van der Kaaij R.T.
        • Boot H.
        • et al.
        Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy versus palliative systemic chemotherapy in stomach cancer patients with peritoneal dissemination, the study protocol of a multicentre randomised controlled trial (PERISCOPE II).
        BMC Cancer. 2019; 19
      3. Prophylactic Preoperative HIPEC in Advanced Gastric Cancer at High Risk of Peritoneal Recurrence - Full Text View -
        (Available at:) (Accessed May 9, 2022)
        • Götze T.O.
        • Piso P.
        • Lorenzen S.
        • et al.
        Preventive HIPEC in combination with perioperative FLOT versus FLOT alone for resectable diffuse type gastric and gastroesophageal junction type II/III adenocarcinoma - the phase III “PREVENT”- (FLOT9) trial of the AIO/CAOGI/ACO.
        BMC Cancer. 2021; 21
        • Girling D.J.
        • Bancewicz J.
        • Clark P.I.
        • et al.
        Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial.
        Lancet. 2002; 359: 1727-1733
        • Allum W.H.
        • Stenning S.P.
        • Bancewicz J.
        • et al.
        Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer.
        J Clin Oncol. 2009; 27: 5062-5067
        • Avid D.
        • Elsen P.K.
        • Obert R.
        • et al.
        Chemotherapy Followed by Surgery Compared with Surgery Alone for Localized Esophageal Cancer.
        N Engl J Med. 2009; 339: 1979-1984
        • Gebski V.
        • Burmeister B.
        • Smithers B.M.
        • et al.
        Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis.
        Lancet Oncol. 2007; 8: 226-234
        • Cunningham D.
        • Allum W.H.
        • Stenning S.P.
        • et al.
        Perioperative Chemotherapy versus Surgery Alone for Resectable Gastroesophageal Cancer From the Departments of Medicine (D. Vol 355.; 2006.
        (Available at:) (Accessed April 20, 2022)
        • Ychou M.
        • Boige V.
        • Pignon J.P.
        • et al.
        Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: An FNCLCC and FFCD multicenter phase III trial.
        J Clin Oncol. 2011; 29: 1715-1721
        • Al-Batran S.E.
        • Homann N.
        • Pauligk C.
        • et al.
        Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial.
        Lancet. 2019; 393: 1948-1957
        • Macdonald J.S.
        • Benedetti J.
        • Smalley S.
        • et al.
        Chemoradiation of resected gastric cancer: A 10-year follow-up of the phase III trial INT0116 (SWOG 9008).
        Am J Clin Oncol. 2009; 27: 4515
        • van Hagen P.
        • Hulshof M.C.C.M.
        • van Lanschot JJB
        • et al.
        Preoperative Chemoradiotherapy for Esophageal or Junctional Cancer.
        N Engl J Med. 2012; 366: 2074-2084
        • Eyck B.M.
        • van Lanschot JJB
        • Hulshof M.C.C.M.
        • et al.
        Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial.
        J Clin Oncol. 2021; 39: 1995-2004
        • Cats A.
        • Jansen E.P.M.
        • van Grieken N.C.T.
        • et al.
        Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial.
        Lancet Oncol. 2018; 19: 616-628
        • Slagter A.E.
        • Jansen E.P.M.
        • van Laarhoven H.W.M.
        • et al.
        CRITICS-II: a multicentre randomised phase II trial of neo-adjuvant chemotherapy followed by surgery versus neo-adjuvant chemotherapy and subsequent chemoradiotherapy followed by surgery versus neo-adjuvant chemoradiotherapy followed by surgery in resectable gastric cancer.
        BMC Cancer. 2018; 18
        • Lee J.
        • Lim D.H.
        • Kim S.
        • et al.
        Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial.
        J Clin Oncol. 2012; 30: 268-273
        • Park S.H.
        • Lim D.H.
        • Sohn T.S.
        • et al.
        A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial.
        Ann Oncol. 2021; 32: 368-374
        • Leong T.
        • Smithers B.M.
        • Michael M.
        • et al.
        TOPGEAR: a randomised phase III trial of perioperative ECF chemotherapy versus preoperative chemoradiation plus perioperative ECF chemotherapy for resectable gastric cancer (an international, intergroup trial of the AGITG/TROG/EORTC/NCIC CTG).
        BMC Cancer. 2015; 15
        • Leong T.
        • Smithers B.M.
        • Haustermans K.
        • et al.
        TOPGEAR: A Randomized, Phase III Trial of Perioperative ECF Chemotherapy with or Without Preoperative Chemoradiation for Resectable Gastric Cancer: Interim Results from an International, Intergroup Trial of the AGITG, TROG, EORTC and CCTG.
        Ann Surg Oncol. 2017; 24: 2252-2258
        • Hoeppner J.
        • Lordick F.
        • Brunner T.
        • et al.
        ESOPEC: prospective randomized controlled multicenter phase III trial comparing perioperative chemotherapy (FLOT protocol) to neoadjuvant chemoradiation (CROSS protocol) in patients with adenocarcinoma of the esophagus (NCT02509286).
        BMC Cancer. 2016; 16
        • Reynolds J.v.
        • Preston S.R.
        • O’Neill B.
        • et al.
        ICORG 10-14: NEOadjuvant trial in Adenocarcinoma of the oEsophagus and oesophagoGastric junction International Study (Neo-AEGIS).
        BMC Cancer. 2017; 17
        • Gravalos C.
        • Jimeno A.
        HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target.
        Ann Oncol. 2008; 19: 1523-1529
        • Gerson J.N.
        • Skariah S.
        • Denlinger C.S.
        • et al.
        Perspectives of HER2-targeting in gastric and esophageal cancer.
        Expert Opin Investig Drugs. 2017; 26: 531-540
        • Bang Y.J.
        • van Cutsem E.
        • Feyereislova A.
        • et al.
        Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial.
        Lancet. 2010; 376: 687-697
        • Safran H.P.
        • Winter K.
        • Ilson D.H.
        • et al.
        Trastuzumab with trimodality treatment for oesophageal adenocarcinoma with HER2 overexpression (NRG Oncology/RTOG 1010): a multicentre, randomised, phase 3 trial.
        Lancet Oncol. 2022; 23: 259-269
        • Fuchs C.S.
        • Tomasek J.
        • Yong C.J.
        • et al.
        Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial.
        Lancet. 2014; 383: 31-39
        • Wilke H.
        • Muro K.
        • van Cutsem E.
        • et al.
        Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial.
        Lancet Oncol. 2014; 15: 1224-1235
        • Al-Batran S.E.
        • Hofheinz R.D.
        • Schmalenberg H.
        • et al.
        Perioperative ramucirumab in combination with FLOT versus FLOT alone for resectable esophagogastric adenocarcinoma (RAMSES/FLOT7): Results of the phase II-portion—A multicenter, randomized phase II/III trial of the German AIO and Italian GOIM.
        Am J Clin Oncol. 2020; 38: 4501
        • Hofheinz R.D.
        • Haag G.M.
        • Ettrich T.J.
        • et al.
        Perioperative trastuzumab and pertuzumab in combination with FLOT versus FLOT alone for HER2-positive resectable esophagogastric adenocarcinoma: Final results of the PETRARCA multicenter randomized phase II trial of the AIO.
        Am J Clin Oncol. 2020; 38: 4502
        • Kojima T.
        • Shah M.A.
        • Muro K.
        • et al.
        Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer.
        J Clin Oncol. 2020; 38: 4138-4148
        • Chin K.
        • Kato K.
        • Cho B.C.
        • et al.
        Three-year follow-up of ATTRACTION-3: A phase III study of nivolumab (Nivo) in patients with advanced esophageal squamous cell carcinoma (ESCC) that is refractory or intolerant to previous chemotherapy.
        Am J Clin Oncol. 2021; 39: 204
        • Kang Y.K.
        • Boku N.
        • Satoh T.
        • et al.
        Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial.
        Lancet. 2017; 390: 2461-2471