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      Intensity modulated radiotherapy (IMRT) with concurrent chemotherapy as definitive treatment of locally advanced esophageal cancer

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          Abstract

          Background

          To report our experience with increased dose intensity-modulated radiation and concurrent systemic chemotherapy as definitive treatment of locally advanced esophageal cancer.

          Patients and methods

          We analyzed 27 consecutive patients with histologically proven esophageal cancer, who were treated with increased-dose IMRT as part of their definitive therapy. The majority of patients had T3/4 and/or N1 disease (93%). Squamous cell carcinoma was the dominating histology (81%). IMRT was delivered in step-and-shoot technique in all patients using an integrated boost concept. The boost volume was covered with total doses of 56-60 Gy (single dose 2-2.14 Gy), while regional nodal regions received 50.4 Gy (single dose 1.8 Gy) in 28 fractions. Concurrent systemic therapy was scheduled in all patients and administered in 26 (96%). 17 patients received additional adjuvant systemic therapy. Loco-regional control, progression-free and overall survival as well as acute and late toxicities were retrospectively analyzed. In addition, quality of life was prospectively assessed according to the EORTC QLQs (QLQ-OG25, QLQ-H&N35 and QLQ-C30).

          Results

          Radiotherapy was completed as planned in all but one patient (96%), and 21 patients received more than 80% of the planned concurrent systemic therapy. We observed ten locoregional failures, transferring into actuarial 1-, 2- and 3-year-locoregional control rates of 77%, 65% and 48%. Seven patients developed distant metastases, mainly to the lung (71%). The actuarial 1-, 2- and 3-year-disease free survival rates were 58%, 48% and 36%, and overall survival rates were 82%, 61% and 56%. The concept was well tolerated, both in the clinical objective examination and also according to the subjective answers to the QLQ questionnaire. 14 patients (52%) suffered from at least one acute CTC grade 3/4 toxicity, mostly hematological side effects or dysphagia. Severe late toxicities were reported in 6 patients (22%), mostly esophageal strictures and ulcerations. Severe side effects to skin, lung and heart were rare.

          Conclusion

          IMRT with concurrent systemic therapy in the definitive treatment of esophageal cancer using an integrated boost concept with doses up to 60 Gy is feasible and yields good results with acceptable acute and late overall toxicity and low side effects to skin, lung and heart.

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          Most cited references34

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          Epidemiology of esophageal cancer.

          This article discusses the incidence, geographic differences, and risk factors for the 2 most common cancers of the esophagus: squamous cell and adenocarcinoma. Copyright © 2012 Elsevier Inc. All rights reserved.
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            Esophageal cancer: epidemiology, pathogenesis and prevention.

            Esophageal cancer is highly aggressive and is a common cancer both worldwide and in the US. In the past two decades, the incidence and mortality of esophageal cancer in the US have both increased, where as the incidence and mortality of other cancers have decreased. Although esophageal squamous cell carcinoma and esophageal adenocarcinoma differ in their histology and epidemiologic distribution, some of their risk factors (e.g. dietary deficiencies and tobacco) and underlying mechanisms of carcinogenesis are the same. Intensive research into risk factors combined with the ability to identify precursor lesions (e.g.squamous dysplasia in esophageal squamous cell carcinoma and Barrett's esophagus in esophageal adenocarcinoma) has paved the way for studies of chemoprevention for esophageal cancer, some of which have shown promising results.
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              Long-term survival outcomes after definitive chemoradiation versus surgery in patients with resectable squamous carcinoma of the esophagus: results from a randomized controlled trial.

              The aim of this study was to report on the 5-year survival outcomes of patients with resectable esophageal carcinoma who were treated by definitive chemoradiotherapy (CRT) or standard esophagectomy. Between July 2000 and December 2004, 81 patients with resectable squamous cell carcinoma of the mid- or lower thoracic esophagus were randomized to receive esophagectomy or definitive CRT. The primary outcome was the overall survival and secondary outcomes included disease-free survival, morbidities and mortalities. Forty-five patients received esophagectomy and 36 patients were treated by definitive CRT. The overall 5-year survival favors CRT but the difference did not reach statistical significance (surgery 29.4% and CRT 50%, P=0.147). A trend to improved 5-year survival was observed for patients suffering from node-positive disease (P=0.061). The 5-year disease-free survival also showed a trend to significance favoring CRT (P=0.068), particularly for patients suffering from node-positive disease (P=0.017). Both the stage of the disease and albumin level were significant predictors to mortality and disease-free survival. Definitive CRT for squamous esophageal carcinoma resulted in comparable long-term survival to surgery. Further large-scale studies would be required to further investigate the role of CRT in node-positive patients. Clinicaltrials.gov identifier: NCT01032967.
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                Author and article information

                Contributors
                f.roeder@dkfz.de
                n.nicolay@dkfz.de
                peter.huber@med.uni-heidelberg.de
                lahlase@aol.com
                vaskoxylakis@steele.mgh.harvard.edu
                t.bostel@dkfz.de
                f.zwicker@dkfz.de
                j.debus@dkfz.de
                c.timke@dkfz.de
                p.huber@dkfz.de
                Journal
                Radiat Oncol
                Radiat Oncol
                Radiation Oncology (London, England)
                BioMed Central (London )
                1748-717X
                29 August 2014
                29 August 2014
                2014
                : 9
                : 1
                : 191
                Affiliations
                [ ]CCU Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
                [ ]Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
                [ ]CCU Molecular and Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany
                [ ]Department of Radiation Oncology, University of Munich (LMU), Munich, Germany
                [ ]Department of Radiation Oncology, Massachusetts General Hospital, Boston, USA
                [ ]Malteser Krankenhaus St. Franziskus-Hospital, Klinik fuer Strahlentherapie, Flensburg, Germany
                Article
                1158
                10.1186/1748-717X-9-191
                4156653
                25175056
                13f06097-0283-4741-b85e-9d5241fc488a
                © Roeder et al.; licensee BioMed Central Ltd. 2014

                This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 28 April 2014
                : 15 August 2014
                Categories
                Research
                Custom metadata
                © The Author(s) 2014

                Oncology & Radiotherapy
                esophageal cancer,imrt,concurrent chemoradiation
                Oncology & Radiotherapy
                esophageal cancer, imrt, concurrent chemoradiation

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