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Multimodality treatment of esophagus cancer: current status and future perspectives in the United States

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Abstract

Investigations over the past three decades have resulted in multimodality therapy as the standard of care today for the management of stage II and III esophageal cancer in the United States. During this same time period, there has been a shift in the dominant histology and primary location from squamous cell cancer of the midesophagus to adenocarcinoma of the distal esophagus and gastro-esophageal junction. The results of large clinical trials and meta-analyses demonstrate that trimodality therapy (chemoradiation followed by esophagectomy) improves local-regional control and overall survival compared to either single-modality surgery or the sequence of chemotherapy followed by surgery. Concomitant chemoradiation without surgery improves survival and local-regional control compared to radiotherapy alone in patients with squamous cell histology. Thus, surgical and nonsurgical approaches are available for treatment of esophageal cancer in the United States. Current investigations focus on the integration of biologics into current therapies and the identification of prognostic and predictive biomarkers.

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References

  1. Pohl H, Welch HG. The role of overdiagnosis and reclassification in the marked increase of esophageal adenocarcinoma incidence. J Natl Cancer Institute 2005;97(2):142–146.

    Google Scholar 

  2. Birkmeyer JD, Stukel TA, Siewers AE, Goodney PP, Wennberg DE, Lucas FL. Surgeon volume and operative mortality in the United States. N Engl J Med 2003;349(22):2117–2127.

    Article  CAS  PubMed  Google Scholar 

  3. Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, et al. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med 1998;339(27):1979–1984.

    Article  CAS  PubMed  Google Scholar 

  4. Medical Research Council: Surgical resection with or without preoperative chemotherapy in oesophageal cancer. A randomised controlled trial. Lancet 2002;359:1727–1733.

    Google Scholar 

  5. Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, et al. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med 2006;355(1):11–20.

    Article  CAS  PubMed  Google Scholar 

  6. Siewert JR, Stein HJ, Feith M, Bruecher BL, Bartels H, Fink U. Histologic tumor type is an independent prognostic parameter in esophageal cancer: lesson from more than 1000 consecutive resections at a single center in the Western world. Ann Surg 2001;234(3).

  7. Doty JR, Salazar JD, Forastiere AA, Heath EI, Kleinberg L, Heitmiller RF. Postesophagectomy morbidity, mortality, and length of hospital stay after preoperative chemoradiation therapy. Ann Thorac Surg 2002;74(1):227–231; discussion 31.

    Article  PubMed  Google Scholar 

  8. Cooper JS, Guo MD, Herskovic A, MacDonald JS, Martenson JA Jr, Al-Sarraf M, et al. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA 1999;281(17):1623–1627.

    Article  CAS  PubMed  Google Scholar 

  9. Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, et al. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med 1992;326(24):1593–1598.

    Article  CAS  PubMed  Google Scholar 

  10. Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol 2002;20(5):1167–1174.

    Article  CAS  PubMed  Google Scholar 

  11. Rebecca WO, Richard MA. Combined chemotherapy and radiotherapy (without surgery) compared with radiotherapy alone in localized carcinoma of the esophagus. Cochrane Database of Systematic Reviews (online) 2003 (1):CD002092.

  12. Kleinberg L, Forastiere AA. Chemoradiation in the management of esophageal cancer. J Clin Oncol 2007;25(26):4110–4117.

    Article  CAS  PubMed  Google Scholar 

  13. Bedenne L, Michel P, Bouche O, Milan C, Mariette C, Conroy T, et al. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol 2007;25(10):1160–1168.

    Article  CAS  PubMed  Google Scholar 

  14. Jouve J, Michel P, Mariette C, Bonnetain F, Bouche O, Conroy T, et al. Outcome of the nonrandomized patients in the FFCD 9102 trial: chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus. Proc Am Soc Clin Oncol 2008;26(15S):226s.

    Google Scholar 

  15. Stahl M, Stuschke M, Lehmann N, Meyer HJ, Walz MK, Seeber S, et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol 2005;23(10):2310–2317.

    Article  PubMed  Google Scholar 

  16. Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001;19(2):305–313.

    CAS  PubMed  Google Scholar 

  17. Bosset JF, Gignoux M, Triboulet JP, Tiret E, Mantion G, Elias D, et al. Chemoradiotherapy followe by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med 1997;337(3):161–167.

    Article  CAS  PubMed  Google Scholar 

  18. Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med 1996;335(7):462–467.

    Article  CAS  PubMed  Google Scholar 

  19. Burmeister BH, Smithers BM, Gebski V, Fitzgerald L, Simes RJ, Devitt P, et al. Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. Lancet Oncol 2005;6(9):659–668.

    Article  PubMed  Google Scholar 

  20. Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, et al. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol 2008;26(7):1086–1092.

    Article  CAS  PubMed  Google Scholar 

  21. Heath EI, Burtness BA, Heitmiller RF, Salem R, Kleinberg L, Krisely JP, et al. Phase II evaluation of preoperative chemoradiation and postoperative adjuvant chemotherapy for squamous cell and adenocarcinoma of the esophagus. J Clin Oncol 2000;18(4):868–876.

    CAS  PubMed  Google Scholar 

  22. Berger AC, Farma J, Scott WJ, Freedman G, Weiner L, Cheng JD, et al. Complete response to neoadjuvant chemoradiotherapy in esophageal carcinoma is associated with significantly improved survival. J Clin Oncol 2005;23(19):4330–4337.

    Article  PubMed  Google Scholar 

  23. Chirieac LR, Swisher SG, Ajani JA, Komaki RR, Correa AM, Morris JS, et al. Posttherapy pathologic stage predicts survival in patients with esophageal carcinoma receiving preoperative chemoradiation. Cancer (Phila) 2005;103(7):1347–1355.

    Article  Google Scholar 

  24. Gebski V, Burmeister B, Smithers BM, Foo K, Zalcberg J, Simes J. Survival benefits from neoadjuvant chemoradiotherapy or chemotherapy in oesophageal carcinoma: a meta-analysis. Lancet Oncol 2007;8(3):226–234.

    Article  CAS  PubMed  Google Scholar 

  25. Khushalani NI, Leichman CG, Proulx G, Nava H, Bodnar L, Klippenstein D, et al. Oxaliplatin in combination with protractedinfusion fluorouracil and radiation: report of a clinical trial for patients with esophageal cancer. J Clin Oncol 2002;20(12):2844–2850.

    Article  CAS  PubMed  Google Scholar 

  26. Burmeister BH, Walpole ET, D’Arcy N, Burmeister EA, Cox S, Thomson DB, et al. A phase II trial of chemoradiation therapy with weekly oxaliplatin and protracted infusion of 5-fluorouracil for esophageal cancer. Invest New Drugs 2009;27(3):275–279.

    Article  CAS  PubMed  Google Scholar 

  27. Kleinberg L, Powell ME, Forastiere A, Keller S, Anne P, Benson AB. Survival outcome of E1201: an Eastern Cooperative Oncology Group (ECOG) randomized phase II trial of neoadjuvant preoperative paclitaxel/cisplatin/radiotherapy (RT) or irinotecan/cisplatin/RT in endoscopy with ultrasound (EUS) staged esophageal adenocarcinoma. Proc Am Soc Clin Oncol 2008;26(15S):220s.

    Google Scholar 

  28. Ilson DH, Bains M, Kelsen DP, O’Reilly E, Karpeh M, Coit D, et al. Phase I trial of escalating-dose irinotecan given weekly with cisplatin and concurrent radiotherapy in locally advanced esophageal cancer. J Clin Oncol 2003;21(15):2926–2932.

    Article  CAS  PubMed  Google Scholar 

  29. Aklilu M, Ilson DH. Targeted agents and esophageal cancer — the next step? Semin Radiat Oncol 2007;17(1):62–69.

    Article  PubMed  Google Scholar 

  30. Shah MA, Ramanathan RK, Ilson DH, Levnor A, D’Adamo D, O’Reilly E, et al. Multicenter phase II study of irinotecan, cisplatin, and bevacizumab in patients with metastatic gastric or gastroesophageal junction adenocarcinoma. J Clin Oncol 2006;24(33):5201–5206.

    Article  CAS  PubMed  Google Scholar 

  31. Pande AU, Iyer RV, Rani A, Maddipatla S, Yang GY, Nwogu CE, et al. Epidermal growth factor receptor-directed therapy in esophageal cancer. Oncology 2007;73(5–6):281–289.

    Article  CAS  PubMed  Google Scholar 

  32. Gibson MK, Abraham SC, Wu TT, Burtness B, Heitmiller RF, Heath E, et al. Epidermal growth factor receptor, p53 mutation, and pathological response predict survival in patients with locally advanced esophageal cancer treated with preoperative chemoradiotherapy. Clin Cancer Res 2003;9(17):6461–6468.

    CAS  PubMed  Google Scholar 

  33. Izzo JG, Correa AM, Wu TT, Malhotra U, Chao CK, Luthra R, et al. Pretherapy nuclear factor-kappaB status, chemoradiation resistance, and metastatic progression in esophageal carcinoma. Mol Cancer Ther 2006;5(11):2844–2850.

    Article  CAS  PubMed  Google Scholar 

  34. Yoon HH, Powell ME, Murphy K, Montgomery EA, Hatez MJ, Liu G, et al. Outcome prediction based on single nucleotide polymorphisms (SNPs) in DNA repair paths in patients (pts) with esophageal adenocarcinoma (EAC) treated with preoperative (preop) cisplatin (C)-based chemoradiation (CRT): results from the Eastern Cooperative Oncology Group (ECOG). Proc Am Soc Clin Oncol 2009;27(15S):209s.

    Google Scholar 

  35. Yoon HH, Murphy KM, Gibson MK. Clinical outcome prediction in esophageal adenocarcinoma based on tumor and germline single nucleotide polymorphisms in DNA-repair pathways. Proc Am Soc Clin Oncol 2007;25(18S).

  36. Wu X, Gu J, Wu TT, Swisher SG, Liao Z, Correa AM, et al. Genetic variations in radiation and chemotherapy drug action pathways predict clinical outcomes in esophageal cancer. J Clin Oncol 2006;24(23):3789–3798.

    Article  CAS  PubMed  Google Scholar 

  37. Metzger R, Leichman CG, Danenberg KD, Danenberg PV, Lenz HJ, Hayashi K, et al. ERCC1 mRNA levels complement thymidylate synthase mRNA levels in predicting response and survival for gastric cancer patients receiving combination cisplatin and fluorouracil chemotherapy. J Clin Oncol 1998;16(1):309–316.

    CAS  PubMed  Google Scholar 

  38. Brock MV, Gou M, Akiyama Y, Muller A, Wu TT, Montogomery E, et al. Prognostic importance of promoter hypermethylation of multiple genes in esophageal adenocarcinoma. Clin Cancer Res 2003;9(8):2912–2919.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Oncology, Johns Hopkins University School of Medicine, 1650 Orleans Street, G-90, Baltimore, MD, 21231, USA

    Arlene A. Forastiere

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  1. Arlene A. Forastiere
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Correspondence to Arlene A. Forastiere.

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Forastiere, A.A. Multimodality treatment of esophagus cancer: current status and future perspectives in the United States. Esophagus 7, 1–6 (2010). https://doi.org/10.1007/s10388-009-0226-8

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  • DOI: https://doi.org/10.1007/s10388-009-0226-8

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