This Article Full Text Full Text (PDF) Publisher's Note Erratum (v24,p531) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Stahl, M. Articles by Wilke, H. Search for Related Content PubMed PubMed Citation Articles by Stahl, M. Articles by Wilke, H. Social Bookmarking                            What's this?

Chemoradiation With and Without Surgery in Patients With Locally Advanced Squamous Cell Carcinoma of the Esophagus

From the Departments of Medical Oncology and Hematology and Surgery, Kliniken Essen-Mitte; Institute for Medical Informatics, Biometry and Epidemiology, Department of Radiation Oncology, and Department of Internal Medicine (Cancer Research), West German Cancer Center, University of Essen Medical School, Essen; Department of Surgery, Klinikum Solingen, Solingen; Departments of Gastorenterology, Radiation Oncology, and Surgery, University Clinic, Tübingen; and Departments of Gastroenterology, Radiation Oncology, and Surgery, University Clinic, Düsseldorf, Germany

Address reprint requests to M. Stahl, MD, Department of Medical Oncology and Hematology, Kliniken Essen-Mitte, Henricistr 92, D-45136 Essen, Germany; e-mail: m.stahl{at}kliniken-essen-mitte.de

PURPOSE: Combined chemoradiotherapy with and without surgery are widely accepted alternatives for the curative treatment of patients with locally advanced esophageal cancer. The value of adding surgery to chemotherapy and radiotherapy is unknown.

PATIENTS AND METHODS: Patients with locally advanced squamous cell carcinoma (SCC) of the esophagus were randomly allocated to either induction chemotherapy followed by chemoradiotherapy (40 Gy) followed by surgery (arm A), or the same induction chemotherapy followed by chemoradiotherapy (at least 65 Gy) without surgery (arm B). Primary outcome was overall survival time.

RESULTS: The median observation time was 6 years. The analysis of 172 eligible, randomized patients (86 patients per arm) showed overall survival to be equivalent between the two treatment groups (log-rank test for equivalence, P < .05). Local progression-free survival was better in the surgery group (2-year progression-free survival, 64.3%; 95% CI, 52.1% to 76.5%) than in the chemoradiotherapy group (2-year progression-free survival, 40.7%; 95% CI, 28.9% to 52.5%; hazard ratio [HR] for arm B v arm A, 2.1; 95% CI, 1.3 to 3.5; P = .003). Treatment-related mortality was significantly increased in the surgery group than in the chemoradiotherapy group (12.8% v 3.5%, respectively; P = .03). Cox regression analysis revealed clinical tumor response to induction chemotherapy to be the single independent prognostic factor for overall survival (HR, 0.30; 95% CI, 0.19 to 0.47; P < .0001).

CONCLUSION: Adding surgery to chemoradiotherapy improves local tumor control but does not increase survival of patients with locally advanced esophageal SCC. Tumor response to induction chemotherapy identifies a favorable prognostic group within these high-risk patients, regardless of the treatment group.

Supported by the Stiftung Deutsche Krebshilfe.

Presented in part at the 37th Annual Meeting of the American Society of Clinical Oncology, San Francisco, CA, May 12-15, 2001; and at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 3, 2003.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				D.G. Power and D.H. Ilson Review: Integration of targeted agents in the neo-adjuvant treatment of gastro-esophageal cancers Therapeutic Advances in Medical Oncology, November 1, 2009; 1(3): 145 - 165. [Abstract] [PDF]

				T. Ruhstaller, L. Widmer, J. C. Schuller, A. Roth, V. Hess, W. Mingrone, R. von Moos, M. Borner, B. C. Pestalozzi, S. BalmerMajno, et al. Multicenter phase II trial of preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02) Ann. Onc., September 1, 2009; 20(9): 1522 - 1528. [Abstract] [Full Text] [PDF]

				L. Yu, W. K. K. Wu, Z. J. Li, Q. C. Liu, H. T. Li, Y. C. Wu, and C. H. Cho Enhancement of Doxorubicin Cytotoxicity on Human Esophageal Squamous Cell Carcinoma Cells by Indomethacin and 4-[5-(4-Chlorophenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide (SC236) via Inhibiting P-Glycoprotein Activity Mol. Pharmacol., June 1, 2009; 75(6): 1364 - 1373. [Abstract] [Full Text] [PDF]

				M. Stahl, J. Oliveira, and On behalf of the ESMO Guidelines Working Group Esophageal cancer: ESMO Clinical Recommendations for diagnosis, treatment and follow-up Ann. Onc., May 1, 2009; 20(suppl_4): iv32 - iv33. [Full Text] [PDF]

				T. YOSHIDA, T. MIYOSHI, J.-I. SEIKE, H. YAMAI, H. TAKECHI, Y. YUASA, and A. TANGOKU Gene Expression Changes in a Chemoresistant Model with Human Esophageal Cancer Xenografts Using cDNA Microarray Anticancer Res, April 1, 2009; 29(4): 1163 - 1168. [Abstract] [Full Text] [PDF]

				C. G. Willett and B. G. Czito Combined-modality Therapy for Esophageal Cancer ASCO Educational Book, January 1, 2009; 2009(1): 243 - 249. [Abstract] [Full Text] [PDF]

				E. C. Paulson, J. Ra, K. Armstrong, C. Wirtalla, F. Spitz, and R. R. Kelz Underuse of Esophagectomy as Treatment for Resectable Esophageal Cancer Arch Surg, December 1, 2008; 143(12): 1198 - 1203. [Abstract] [Full Text] [PDF]

				X.-B. D'Journo, P. Michelet, L. Dahan, C. Doddoli, J.-F. Seitz, R. Giudicelli, P. A. Fuentes, and P. A. Thomas Indications and outcome of salvage surgery for oesophageal cancer Eur. J. Cardiothorac. Surg., June 1, 2008; 33(6): 1117 - 1123. [Abstract] [Full Text] [PDF]

				J. Tepper, M. J. Krasna, D. Niedzwiecki, D. Hollis, C. E. Reed, R. Goldberg, K. Kiel, C. Willett, D. Sugarbaker, and R. Mayer Phase III Trial of Trimodality Therapy With Cisplatin, Fluorouracil, Radiotherapy, and Surgery Compared With Surgery Alone for Esophageal Cancer: CALGB 9781 J. Clin. Oncol., March 1, 2008; 26(7): 1086 - 1092. [Abstract] [Full Text] [PDF]

				D. H. Ilson Combined Modality Therapy for Gastric, Esophageal, and Gastroesophageal Junction Cancers ASCO Educational Book, January 1, 2008; 2008(1): 177 - 182. [Abstract] [Full Text] [PDF]

				G. Crehange, P. Maingon, K. Peignaux, T. D. N'guyen, X. Mirabel, C. Marchal, P. Verrelle, B. Roullet, F. Bonnetain, and L. Bedenne Phase III Trial of Protracted Compared With Split-Course Chemoradiation for Esophageal Carcinoma: Federation Francophone de Cancerologie Digestive 9102 J. Clin. Oncol., November 1, 2007; 25(31): 4895 - 4901. [Abstract] [Full Text] [PDF]

				L. Kleinberg and A. A. Forastiere Chemoradiation in the Management of Esophageal Cancer J. Clin. Oncol., September 10, 2007; 25(26): 4110 - 4117. [Abstract] [Full Text] [PDF]

				M. Gotoh, H. Takiuchi, S.-i. Kawabe, S. Ohta, T. Kii, S. Kuwakado, and K.-i. Katsu Epidermal Growth Factor Receptor is a Possible Predictor of Sensitivity to Chemoradiotherapy in the Primary Lesion of Esophageal Squamous Cell Carcinoma Jpn. J. Clin. Oncol., September 1, 2007; 37(9): 652 - 657. [Abstract] [Full Text] [PDF]

				L. Bedenne and F. Bonnetain In Reply J. Clin. Oncol., September 1, 2007; 25(25): 4026 - 4027. [Full Text] [PDF]

				D. P. Kelsen, K. A. Winter, L. L. Gunderson, J. Mortimer, N. C. Estes, D. G. Haller, J. A. Ajani, W. Kocha, B. D. Minsky, J. A. Roth, et al. Long-Term Results of RTOG Trial 8911 (USA Intergroup 113): A Random Assignment Trial Comparison of Chemotherapy Followed by Surgery Compared With Surgery Alone for Esophageal Cancer J. Clin. Oncol., August 20, 2007; 25(24): 3719 - 3725. [Abstract] [Full Text] [PDF]

				T. Kii, H. Takiuchi, S. Kawabe, M. Gotoh, S. Ohta, T. Tanaka, S. Kuwakado, H. Nishitani, and K.-i. Katsu Evaluation of Prognostic Factors of Esophageal Squamous Cell Carcinoma (Stage II III) After Concurrent Chemoradiotherapy Using Biopsy Specimens Jpn. J. Clin. Oncol., August 20, 2007; (2007) hym077v1. [Abstract] [Full Text] [PDF]

				S. Y. Kang, J. H. Han, K. J. Lee, J.-H. Choi, J. I. Park, H. I. Kim, H.-W. Lee, J. H. Jang, J. S. Park, H. C. Kim, et al. Low Expression of Bax Predicts Poor Prognosis in Patients with Locally Advanced Esophageal Cancer Treated with Definitive Chemoradiotherapy Clin. Cancer Res., July 15, 2007; 13(14): 4146 - 4153. [Abstract] [Full Text] [PDF]

				D. H. Ilson Surgery After Primary Chemoradiotherapy in Squamous Cancer of the Esophagus: Is the Photon Mightier Than the Sword? J. Clin. Oncol., April 1, 2007; 25(10): 1155 - 1156. [Full Text] [PDF]

				L. Bedenne, P. Michel, O. Bouche, C. Milan, C. Mariette, T. Conroy, D. Pezet, B. Roullet, J.-F. Seitz, J.-P. Herr, et al. Chemoradiation Followed by Surgery Compared With Chemoradiation Alone in Squamous Cancer of the Esophagus: FFCD 9102 J. Clin. Oncol., April 1, 2007; 25(10): 1160 - 1168. [Abstract] [Full Text] [PDF]

				A. J. Graham, F. M. Shrive, W. A. Ghali, B. J. Manns, S. C. Grondin, R. J. Finley, and J. Clifton Defining the Optimal Treatment of Locally Advanced Esophageal Cancer: A Systematic Review and Decision Analysis Ann. Thorac. Surg., April 1, 2007; 83(4): 1257 - 1264. [Abstract] [Full Text] [PDF]

				L Rubbia-Brandt, E Giostra, C Brezault, A. Roth, A Andres, V Audard, P Sartoretti, B Dousset, P. Majno, O Soubrane, et al. Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery Ann. Onc., February 1, 2007; 18(2): 299 - 304. [Abstract] [Full Text] [PDF]

				C-C Lin, C-H Hsu, J. Cheng, H-P Wang, J-M Lee, K-H Yeh, C-H Yang, J-T Lin, A-L Cheng, and Y-C Lee Concurrent chemoradiotherapy with twice weekly paclitaxel and cisplatin followed by esophagectomy for locally advanced esophageal cancer Ann. Onc., January 1, 2007; 18(1): 93 - 98. [Abstract] [Full Text] [PDF]

				F. Bonnetain, O. Bouche, P. Michel, C. Mariette, T. Conroy, D. Pezet, B. Roullet, J.-F. Seitz, B. Paillot, P. Arveux, et al. A comparative longitudinal quality of life study using the Spitzer quality of life index in a randomized multicenter phase III trial (FFCD 9102): chemoradiation followed by surgery compared with chemoradiation alone in locally advanced squamous resectable thoracic esophageal cancer Ann. Onc., May 1, 2006; 17(5): 827 - 834. [Abstract] [Full Text] [PDF]

				S.-c. Zhang, S. Hironaka, A. Ohtsu, S. Yoshida, T. Hasebe, M. Fukayama, and A. Ochiai Computer-assisted analysis of biopsy specimen microvessels predicts the outcome of esophageal cancers treated with chemoradiotherapy. Clin. Cancer Res., March 15, 2006; 12(6): 1735 - 1742. [Abstract] [Full Text] [PDF]

				J. G. Izzo, U. Malhotra, T.-T. Wu, J. Ensor, R. Luthra, J. H. Lee, S. G. Swisher, Z. Liao, K.S. C. Chao, W. N. Hittelman, et al. Association of Activated Transcription Factor Nuclear Factor {kappa}B With Chemoradiation Resistance and Poor Outcome in Esophageal Carcinoma J. Clin. Oncol., February 10, 2006; 24(5): 748 - 754. [Abstract] [Full Text] [PDF]

				T. Ruhstaller, A. Mueller, D. Koeberle, and B. Thuerlimann Is There Really Enough Evidence to Abandon Surgery After Radiation Chemotherapy in Esophageal Cancer? J. Clin. Oncol., November 20, 2005; 23(33): 8547 - 8548. [Full Text] [PDF]