Multimodality Therapy for Adenocarcinoma of the Esophagus, Gastric Cardia, and Upper Gastric Third

  • John V. ReynoldsEmail author
  • Thomas J. Murphy
  • Narayamasamy Ravi
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 182)


There is considerable controversy over the level of recommendations from randomized trials underpinning management decisions for patients presenting with localized adenocarcinoma of the esophagus and esophagogastric junction. Despite a paucity of Level 1 recommendations compared with other gastrointestinal sites, in particular rectal cancer, there is an emerging consensus in practice to consider multimodal approaches in all cases that present with T3 or node-positive disease. There is also an optimism that new approaches, including response prediction based on sequential 18FDG-PET scanning following induction chemotherapy, and novel drugs targeted at EGF, EGFR, VEGF, and tyrosine kinase inhibition may improve treatment pathways and outcomes. In this review, we assess the level of recommendations from the major published trials and ­discuss new trials and approaches.


Vascular Endothelial Growth Factor Esophageal Adenocarcinoma Squamous Cell Cancer Esophageal Squamous Cell Cancer Advanced Esophageal Cancer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Birkmeyer JD, Siewers AE, Finlayson EV, Stukel TA et al (2002) Hospital volume and surgical mortality in the United States. N Engl J Med 346:1128–1137PubMedCrossRefGoogle Scholar
  2. Blot WJ, De Vesa SS, Kneller RW, Fraumeni JF Jr (1991) Rising incidence of adenocarcinoma of the oesophagus and gastric cardia. JAMA 265: 1287–1289PubMedCrossRefGoogle Scholar
  3. Bosset J-F, Gignoux M, Tiboulet J-P et al (1997) Chemoradiotherapy followed by surgery compared with surgery alone in squamous cell cancer of the esophagus. N Engl J Med 337:161–167PubMedCrossRefGoogle Scholar
  4. Burmeister BH, Smithers BM, Gebski V, Fitzgerald L et al (2005) Surgery alone versus chemoradiotherapy followed by surgery for respectable cancer of the oesophagus: a randomised controlled phase III trial. Lancet Oncol 6:659–668PubMedCrossRefGoogle Scholar
  5. Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Muese M, Harstrick A, Verslype C, Chau I, Van Cutsem E (2004) Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 351:337–345PubMedCrossRefGoogle Scholar
  6. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants (2006) Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 355:11–20Google Scholar
  7. Cunningham D, Starling N, Rao S, Iveson T et al (2008) Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med 358: 36–46PubMedCrossRefGoogle Scholar
  8. Daly JM (2000) Esophageal cancer: results of an American College of Surgeons Patient Care Evaluation Study. J Am Coll Surg 190:562–572PubMedCrossRefGoogle Scholar
  9. Enzinger PC, Mayer RJ (2003) Esophageal Cancer. N Engl J Med 349:2241–2252PubMedCrossRefGoogle Scholar
  10. Ferry DR, Anderson M, Beddard K, Tomlinson S, Atherfold P, Obszynska J, Harrison R, Jankowski J (2007) A phase II study of gefitinib monotherapy in advanced esophageal adenocarcinoma: evidence of gene expression, cellular, and clinical response. Clin Cancer Res 13: 5869–5875PubMedCrossRefGoogle Scholar
  11. Fiorica F, DiBona D, Schepis F, Licata A, Shahied L et al (2004) Preoperative chemoradiotherapy for oesophageal cancer: a systematic review and meta-analysis. Gut 53:925–930PubMedCrossRefGoogle Scholar
  12. Gebski V, Burmeister B, Smithers BM, Foo K, Zalcberg J, Simes J; Australasian Gastro-Intestinal Trials Group (2007) Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol 8:226–234Google Scholar
  13. Geh JI, Crellin AM, Glynne-Jones R (2001) Preoperative (neoadjuvant) chemoradiotherapy in oesophageal cancer. Br J Surg 88:338–356PubMedCrossRefGoogle Scholar
  14. Gillham CM, Lucey JA, Keogan M, Duffy GJ, et al (2006) (18) FDG uptake during induction chemoradiation for oesophageal cancer fails to predict histomorphological tumour response. Br J Cancer 95: 1174–1179PubMedCrossRefGoogle Scholar
  15. Habr-Gama A, Perez RO, Nadalin W, Sabbago J et al (2004) Operative versus nonoperative treatment for Stage 0 distal rectal cancer following chemoradiation therapy. Long term results. Ann Surg 240:711–718PubMedGoogle Scholar
  16. Kelsen DP, Ginsberg R, Pajak TF et al (1998) Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med 339:1974–1984CrossRefGoogle Scholar
  17. Kleespies A, Guba M, Jauch KW, Bruns CJ (2004) Vascular endothelial growth factor in esophageal cancer. Surg Oncol 87(2):95–104CrossRefGoogle Scholar
  18. Lee HK, Vapociyan AA, Cox JD, Tucker SL et al (2003) Postoperative pulmonary complications after preoperative chemoradiation for esophageal carcinoma: correlation with pulmonary dose-volume histogram parameters. Int J Radiat Oncol Biol Phys 57:1317–1322PubMedCrossRefGoogle Scholar
  19. Lordick F, Ott K, Krause BJ, Weber WA, Becker K, Stein HJ, Lorenzen S, Schuster T, Wieder H, Herrmann K, Bredenkamp R, Höfler H, Fink U, Peschel C, Schwaiger M, Siewert JR (2007) PET to assess early metabolic response and to guide treatment of adenocarcinoma of the oesophagogastric junction: the MUNICON phase II trial. Lancet Oncol 8(9):797–805PubMedCrossRefGoogle Scholar
  20. Macdonald JS, Smalley SR, Benedetti J, Hundahl SA et al (2001) Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of stomach or gastroesophageal junction. N Engl J Med 345:725–730PubMedCrossRefGoogle Scholar
  21. Mariette C, Piessen G, Triboulet JP (2007) Therapeutic strategies in oesophageal carcinoma: role of ­surgery and other modalities. Lancet Oncol 8:545–553PubMedCrossRefGoogle Scholar
  22. Medical Research Council Oesophageal Cancer Working Group (2002) Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet 359:1727–1733CrossRefGoogle Scholar
  23. Ott K, Weber WA, Lordick F, Becker K, Busch R, Herrmann K, Wieder H, Fink U, Schwaiger M, Siewert JR (2006) Metabolic imaging predicts response, survival, and recurrence in adenocarcinomas of the esophagogastric junction. J Clin Oncol 10(24):4692–4698CrossRefGoogle Scholar
  24. Peters CJ, Fitzgerald RC (2007) Systematic review: the application of molecular pathogenesis to prevention and treatment of oesophageal adenocarcinoma. Aliment Pharmacol Ther 25:1253–1269PubMedCrossRefGoogle Scholar
  25. Portale G, Hagen JA, Peters JH, Chan LS et al (2006) Modern 5-year survival of respectable esophageal adenocarcinoma: single institution experience with 263 patients. J Am Coll Surg 202: 588–596PubMedCrossRefGoogle Scholar
  26. Presta LG, Chen H, O’Connor SJ, Chisholm V, Meng YG, Krummen L, Winkler M, Ferrara N (1997) Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders. Cancer Res 57(20):4593–4599PubMedGoogle Scholar
  27. Reynolds JV, Ravi N, Hollywood D, Kennedy MJ, Rowley SM, Ryan A, Hughes N, Carey M, Byrne P (2006) Neoadjuvant chemoradiation may increase the risk of respiratory complications and sepsis after transthoracic esophagectomy. J Thorac Cardiovasc Surg 132:549–555PubMedCrossRefGoogle Scholar
  28. Reynolds JV, Muldoon C, Hollywood D, Ravi N, Rowley S, O’Byrne K, Kennedy MJ, Murphy TJ (2007) Long-term outcomes following neoadjuvant chemoradiotherapy for oesophageal cancer. Ann Surg 245:707–716PubMedCrossRefGoogle Scholar
  29. Safran H, Suntharalingam M, Dipetrillo T, Ng T, Doyle LA, Krasna M, Plette A, Evans D, Wanebo H, Akerman P, Spector J, Kennedy N, Kennedy T (2008) Cetuximab with concurrent chemoradiation for esophagogastric cancer: assessment of toxicity. Int J Radiat Oncol Biol Phys 70:391–395PubMedCrossRefGoogle Scholar
  30. Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351: 1731–1740PubMedCrossRefGoogle Scholar
  31. Shah MA, Ramanathan RK, Ilson DH, Levnor A, D’Adamo D, O’Reilly E, Tse A, Trocola R, Schwartz L, Capanu M, Schwartz GK, Kelsen DP (2006) Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol 24:5201–5206PubMedCrossRefGoogle Scholar
  32. Siewert JR, Stein HJ (1998) Classification of adenocarcinoma of the oesophago-gastric junction. Br J Surg 85:1457–1459PubMedCrossRefGoogle Scholar
  33. Siewert JR, Feith M, Werner M, Stein HJ (2000) Adenocarcinoma of the esophagastric junction: results of surgical therapy based on anatomical/topographical classification in 1002 consecutive patients. Ann Surg 232:353–361CrossRefGoogle Scholar
  34. Suntharalingam M, Mougham J, Coia LR et al (1999) The national practice for patients receiving radiation therapy for carcinoma of the esophagus: results of the 1996-1999 Patterns of Care Study. Cancer 85:2499–2505CrossRefGoogle Scholar
  35. Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D, Mayer R (2008) Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol 26:1086–1092PubMedCrossRefGoogle Scholar
  36. Urba SG, Orriner MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M (2001) Randomised trial of preoperative chemoradiotherapy versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 19:305–313PubMedGoogle Scholar
  37. van de Schoot L, Romme EA, van der Sangen MJ, Creemers GJ, van Lijnschoten G, van Driel OJ, Rutten HJ, Nieuwenhuijzen GA (2008) A highly active and tolerable neoadjuvant regimen combining paclitaxel, carboplatin, 5-FU, and radiation therapy in patients with stage II and III esophageal cancer. Ann Surg Oncol 15:88–95PubMedCrossRefGoogle Scholar
  38. Walsh T, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TPJ (1996) A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 335:462–467PubMedCrossRefGoogle Scholar
  39. Wayman J, Bennett MK, Raimes SA, Griffin SM (2002) The pattern of recurrence of adenocarcinoma of the oesophago-gastric junction. Br J Cancer 86(8):1223–1229PubMedCrossRefGoogle Scholar
  40. Weber WA, Ott K, Becker K, Dittler HJ et al (2001) Prediction of response to preoperative chemotherapy in adenocarcinomas of the esophagogastric junction by metabolic imaging. J Clin Oncol 19:3058–3065PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • John V. Reynolds
    • 1
    Email author
  • Thomas J. Murphy
  • Narayamasamy Ravi
  1. 1.Department of SurgeryTrinity Centre, St. James’s HospitalDublin 8Ireland

Personalised recommendations