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      Multidisciplinary Modalities Achieve Encouraging Long-Term Survival in Resectable Limited-Disease Esophageal Small Cell Carcinoma

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          Abstract

          Background

          The management of limited-disease esophageal small cell carcinoma is not well defined, and the role of surgery is still controversial. We aim to determine the optimal treatment strategy in limited-disease of esophageal small cell carcinoma.

          Methods and Findings

          We conducted a retrospective review of 141 patients with limited-disease esophageal small cell carcinoma from 3 institutions in China who underwent treatment between July 1994 and September 2008, July 1994 and July 2011, and June 2004 and December 2010, respectively. The survival rate was calculated by the Kaplan-Meier method, and the log-rank test was used to assess the survival differences between the groups. Cox proportional hazards model were used to further determine the independent factors impacting overall survival. The median survival time was 16.1 months for the entire cohort of patients, with a 5-year survival rate of 6.7%. The median survival times for surgery alone, surgery combined with chemotherapy, surgery combined with radiotherapy, surgery combined with chemotherapy and radiotherapy, chemotherapy plus radiotherapy, and chemotherapy alone were 18.0 months, 15.0 months, 23.0 months, 25.0 months, 17.1 months, and 6.1 months, respectively; the corresponding 5-year survival rates were 0%, 15.4%, 0%, 38.9%, 0%, and 0%, respectively. For the 105 patients who underwent R0 resection, the median disease-free survival time was 12.0 months, with a 95% confidence interval of 9.5 months to 14.5 months. The multivariate Cox regression analysis demonstrated that advanced pathological staging ( p = 0.003), and pure esophageal small cell carcinoma ( p = 0.035) were independent factors decreasing overall survival.

          Conclusions

          Our data suggested that multidisciplinary modalities achieved encouraging long-term survival in patients with resectable limited-disease of esophageal small cell carcinoma.

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          Most cited references25

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          Staging small cell lung cancer: Veterans Administration Lung Study Group versus International Association for the Study of Lung Cancer--what limits limited disease?

          Small cell lung cancer (SCLC) is usually classified into a two-stage system, limited (LD) and extensive disease (ED). However, the criteria for these two categories remain controversial. The widely used Veterans Administration Lung Study Group (VALG) definition of LD includes patients with primary tumor and nodal involvement limited to one hemithorax. In contrast, the International Association for the Study of Lung Cancer (IASLC) recommends that LD should additionally include all patients without distant metastasis. As a consequence, since treatment modalities for LD and ED could be different, individual clinical outcome of SCLC patients may be influenced by the staging system chosen. Among 109 consecutive SCLC patients treated in our clinic between 1989 and 1999 (mean age 68+/-9.1 years, 81% male) 23 patients (21%) could be either classified as LD or ED (LD-ED), depending on the staging system used. The prognosis of this overlapping group (LD-ED: median survival 291 days) was not statistically different from patients with limited disease defined by VALG criteria (LD-VALG: 385 days, log-rank test P = 0.42). On the other hand the survival difference between LD-ED patients and the ED-IASLC population was relevant (ED-IASLC: 208 days, P = 0.05), indicating that LD-ED patients should rather be included in the LD category. This is further supported by the results of a multivariate Cox regression analysis with all clinically relevant data. Only stage as defined by IASLC criteria was an independent prognostic factor in the likelihood-ratio-forward (hazard ratio = 1.94, CI = 1.26-2.99; P = 0.005) and backward model (hazard ratio = 1.76, CI: 1.12-2.76; P = 0.012), confirming the higher discriminatory power of the IASLC definition. In conclusion, the IASLC staging criteria for SCLC patients have a higher prognostic impact and are therefore preferable in clinical practice and future therapeutic trials. Copyright 2002 Elsevier Science Ireland Ltd.
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            A prospective randomized trial to determine the benefit of surgical resection of residual disease following response of small cell lung cancer to combination chemotherapy.

            Three hundred twenty-eight patients with limited stage small cell lung cancer were enrolled in a trial to evaluate surgical treatment for such patients responding to chemotherapy. Cyclophosphamide, doxorubicin, and vincristine were administered every 21 days for five cycles. Patients achieving at least partial response who had confirmation of pure small cell histologic features by pathology review and who were fit enough for thoracotomy were randomized to undergo or not to undergo pulmonary resection. All randomized patients received radiotherapy to the chest and brain. Two hundred seventeen (66%) of the patients achieved objective response (90 complete response; 127 partial response). One hundred forty-six patients were randomized (66% of responders, 44% of all patients): 70 to surgery and 76 to no surgery. Results of surgery were 83% resection rate, 19% pathologic complete remission rate, and 9% with residual non-small cell histologic features only, for a total of 28% eradication of small cell lung cancer. The survival curves for the two arms are not different (log rank p = 0.78). Median survivals were 12 months for all enrolled patients and 16 months for those who were randomized. Actuarial 2-year survival is 20%. The results of this trial do not support the addition of pulmonary resection to the multimodality treatment of small cell lung cancer.
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              Primary small cell carcinoma of the esophagus: a review of the literature with emphasis on therapy and prognosis.

              Few studies of patients with esophageal small cell carcinoma (SCC) have been conducted. Choice of treatment remains controversial. The authors analyzed data on 199 evaluable esophageal SCC patients, selected from among 230 patients found in the literature, and a data extraction form that recorded 11 features was completed. To allow for the evaluation of prognostic factors that influenced survival, the patients were grouped according to limited stage (LS), which was defined as disease confined to the esophagus, or extensive stage (ES), which was defined as disease that had spread beyond locoregional boundaries. Univariate and multivariate analyses were performed. Treatment was categorized as either local or local with systemic; for the ES cases, the categories were defined as treatment versus no treatment. The tumor site was described in 178 cases (89%). Mean tumor size was 6.1. Pure SCC was found in 137 cases (68.8%), whereas 62 cases (31.2%) showed mixed SCC; 93 (46.7%) were LS, whereas 95 (47.7%) were ES. In 11 cases (5.5%), the stage was not determined. There was a significant difference in survival between patients with LS and those with ES (P 60 years, the median survival was 6 months), tumor size (for those with tumors 5 cm, the median survival was 4 months), and type of treatment (with local plus systemic treatment, the median survival was 20 months, whereas with local it was 5 months). In multivariate analysis, tumor size (P = 0.007) and type of treatment (P < 0.001) were shown to be independent predictive variables. Esophageal SCC is an aggressive type of tumor. This study shows that there are significant differences between LS and ES and that in LS, both tumor size and type of treatment are possible prognostic factors.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                9 July 2013
                : 8
                : 7
                : e69259
                Affiliations
                [1 ]Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou City, Guangdong Province, People’s Republic of China
                [2 ]State Key Laboratory of Oncology in South China, Guangzhou City, Guangdong Province, People’s Republic of China
                [3 ]Department of Thoracic Surgery, Linzhou Esophageal Cancer Hospital, Yaocun Town, Linzhou City, Henan Province, People’s Republic of China
                [4 ]Department of Medical Oncology, the First Affiliated Hospital of Xiamen University; Xiamen City, Fujian Province, People’s Republic of China
                [5 ]Department of Thoracic Surgery, Sun Yat-sen University Cancer Center,Guangzhou City, Guangdong Province, People’s Republic of China
                University of Nebraska Medical Center, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: XH HXY. Performed the experiments: XH JCW JXW HXY. Analyzed the data: XH XW HXY. Contributed reagents/materials/analysis tools: PL JHF. Wrote the paper: XH JCW HXY.

                Article
                PONE-D-12-31657
                10.1371/journal.pone.0069259
                3706419
                23874925
                17bdce79-b8db-4fc7-be84-9b369a9bbaf4
                Copyright @ 2013

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 13 October 2012
                : 11 June 2013
                Page count
                Pages: 7
                Funding
                This study was partly supported by the Young Scientists Fund of the National Natural Science Foundation of China (81000935), the Young Teachers’ Training Program of Sun Yat-sen University (11ykpy59), and Guangdong Provincial Science and Technology Planning Foundation (2011B031800179). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine
                Clinical Research Design
                Cohort Studies
                Retrospective Studies
                Gastroenterology and Hepatology
                Esophagus
                Oncology
                Cancers and Neoplasms
                Gastrointestinal Tumors
                Esophageal Cancer
                Lung and Intrathoracic Tumors
                Extrapulmonary Small Cell Carcinoma
                Cancer Treatment
                Surgery
                Surgical Oncology
                Thoracic Surgery

                Uncategorized
                Uncategorized

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