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      OncoTargets and Therapy (submit here)

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      Multimodality therapy is recommended for limited-stage combined small cell esophageal carcinoma


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          Background and aim

          Limited-stage combined small cell esophageal carcinoma (LS-C-SCEC) is a rare, poorly understood, underdiagnosed disease, with components of both small cell esophageal cancer and non–small cell esophageal cancer. We investigated the optimal treatment strategy and prognostic factors in patients with LS-C-SCEC.

          Patients and methods

          LS-C-SCEC patients included in the analysis (from our hospital and the literature) were treated between January 1966 and December 2013. Patient treatment strategies included surgery (S), chemotherapy (CT), and radiation therapy (RT). The primary end point was overall survival (OS); the secondary end points included tumor complete response rates, patterns of failure, and toxicity. Kaplan–Meier curves were compared with the log-rank test. Univariate and multivariate analyses were used to determine prognosticators for OS.


          A total of 72 patients were included in the analysis: 24 (33%) from our hospital and 48 (67%) from the literature. The median OS of all patients was 15.0 months. Patients who received CT had a significantly longer median OS than did those who did not (OS 22.8 months vs 10.0 months) ( P=0.03). Patients treated with multimodality therapy (including RT+CT [18%], S+CT [40%], or S+RT+CT [17%]) vs monotherapy (typically, S [18%]) had significantly improved OS (15.5 months vs 9.3 months) ( P=0.02) and complete response rates. On multivariate analysis, tumor location (upper third of the esophagus) and type of treatment (monotherapy) were the only factors predictive of poor OS.


          Multimodality therapy (including RT+CT, S+CT, or S+RT+CT) improves OS for patients with LS-C-SCEC compared with monotherapy (typically, S). Additional studies are necessary to personalize multimodal treatment approaches to individual patients.

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          Most cited references38

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          Small-cell carcinomas of the gastrointestinal tract: a review.

          To improve our understanding of the entity of small-cell carcinoma (SmCC) of the gastrointestinal (GI) tract. A MEDLINE search was done, using the terms "small cell carcinoma" or "oat cell carcinoma" combined with "gastrointestinal" or with any of the GI sites, for the period 1970 to 2003. The 138 eligible reports identified in this way were reviewed for clinical data. To date, approximately 544 cases of GI SmCC have been reported. The disease represents 0.1% to 1% of all GI malignancies, with the esophagus being the most common primary site. A majority of patients present with overt distant metastases. Systemic symptoms are common; ectopic hormonal secretion may occur. By light microscopy, GI SmCCs are essentially indistinguishable from primary pulmonary SmCC. The presence of non-SmCC components is common. Data from molecular analysis of the disease has identified some similarities to pulmonary SmCC. Chemotherapy represents the main treatment option, with modest impact on survival. In locoregional disease, the literature suggests that treatment be initiated using chemoradiotherapy and then, if metastatic disease is still excluded, surgical resection be considered. The disease is highly aggressive, and survival is in the range of several weeks for untreated patients and of 6 to 12 months for those receiving therapy. SmCC of the GI tract is a rare and lethal disease. Although there are many similarities to pulmonary SmCC, some differences between the two entities are suggested. While chemotherapy can achieve significant palliation, surgery may have a potential impact on long-term survival of patients with locoregional disease.
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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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              Small-cell carcinoma of the esophagus and gastroesophageal junction: review of the Memorial Sloan-Kettering experience.

              Esophageal small-cell carcinoma (SCC) is rare, highly malignant and the optimal treatment approach has not been defined. We report the largest single-institution retrospective review of patients with esophageal and gastroesophageal (GE) junction SCC. Twenty-five patients were identified, with complete records available for 22. Eighty-two percent were male, 82% had pure SCC histology and 86% of tumors were in the lower esophagus or GE junction. On the basis of the Veterans' Administration Lung Study Group criteria, 14 patients (64%) presented with limited disease (LD). Median survival was 19.8 months (range, 1.5 months to 11.2+ years); for LD patients, 22.3 months (range, 6 months to 11.2+ years); for extensive disease (ED) patients, 8.5 months (range, 1.5 months to 2.2 years, P = 0.02). With a median follow-up of 38 months, six patients (27%) are alive, one with ED and five with LD. Two LD patients are alive and free of disease for >5 years. Four of the five LD patients who are long-term survivors received induction chemotherapy followed by chemoradiotherapy without surgery. Our data indicate that patients with LD esophageal SCC treated with induction chemotherapy followed by consolidative chemoradiation can achieve long-term survival. The contribution of surgery remains unclear.

                Author and article information

                Onco Targets Ther
                Onco Targets Ther
                OncoTargets and Therapy
                OncoTargets and therapy
                Dove Medical Press
                13 February 2015
                : 8
                : 437-444
                [1 ]Department of Radiation Oncology, CyberKnife Center, and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin, People’s Republic of China
                [2 ]Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA
                Author notes
                Correspondence: Mao-Bin Meng; Zhi-Yong Yuan, Department of Radiation Oncology and CyberKnife Center, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin 300060, People’s Republic of China, Tel +86 22 2334 1405, Fax +86 22 2334 1405, Email doctormm991@ 123456hotmail.com

                *These authors contributed equally to this work

                © 2015 Wang et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research

                Oncology & Radiotherapy
                esophageal neoplasm,small cell,radiation therapy,surgery,chemotherapy
                Oncology & Radiotherapy
                esophageal neoplasm, small cell, radiation therapy, surgery, chemotherapy


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