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      Aging‐related prognosis analysis of definitive radiotherapy for very elderly esophageal cancer

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          Abstract

          Because of the exclusion for the patients more than 75 years (very elderly patients) in many clinical trials of esophageal cancer ( EC), there is no consensus on prognosis and treatment for this population. We aim to evaluate the outcomes and aging‐related prognostic factors of definitive radiotherapy ( RT) for very elderly EC patients. We retrospectively analyzed 149 very elderly EC patients consecutively treated between January 2015 and June 2016 by definitive intensity‐modulated radiotherapy ( IMRT) with or without chemotherapy. The clinical outcome and toxicities were assessed, and the potential prognostic factors, such as nutritional risk index ( NRI) and neutrophil–lymphocyte ratio ( NLR), were analyzed statistically. The median follow‐up time for survivors was 22.5 months. The 2‐year overall survival ( OS), local–regional failure‐free survival ( LRFFS), and distant metastasis‐free survival ( DMFS) were 51.6%, 54.7%, and 85.2%, respectively. Independent predictors for poorer OS were higher American Joint Committee on Cancer ( AJCC) stage, lower NRI, and higher NLR value before RT. Meanwhile, the total dose (cutoff value 60 Gy) of planning gross tumor volume ( PGTV) and chemotherapy was also identified as independent prognostic indicator for LRFFS and DMFS, respectively. 72 patients had treatment failure and 58 (80.6%), 6 (8.3%), and 18 (25.0%) patients had experienced local, regional, and distant failure, respectively. Few severe toxicities were observed. The conservative definitive RT with modern technique was effective for very elderly EC patients in short term with low rate and tolerable toxicities. Local residue or recurrence was the most common failure pattern. The aging‐related prognostic factors concerned nutrition and immune, such as NRI and NLR before RT, should be considered for use in future clinical practice.

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          Cancer incidence and mortality in China, 2013.

          National Central Cancer Registry of China (NCCRC) updated nationwide statistics of cancer incidence and mortality in China using population-based cancer registration data in 2013 from all available cancer registries.
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            The causes and consequences of cancer-associated malnutrition.

            Cancer-associated malnutrition can result from local effects of a tumour, the host response to the tumour and anticancer therapies. Although cancer patients often have reduced food intake (due to systemic effects of the disease, local tumour effects, psychological effects or adverse effects of treatment), alterations in nutrient metabolism and resting energy expenditure (REE) may also contribute to nutritional status. Several agents produced by the tumour directly, or systemically in response to the tumour, such as pro-inflammatory cytokines and hormones, have been implicated in the pathogenesis of malnutrition and cachexia. The consequences of malnutrition include impairment of immune functions, performance status, muscle function, and quality of life. In addition, responses to chemotherapy are decreased, chemotherapy-induced toxicity and complications are more frequent and severe, and survival times are shortened. Depression, fatigue and malaise also significantly impact on patient well-being. In addition, cancer-related malnutrition is associated with significant healthcare-related costs. Nutritional support, addressing the specific needs of this patient group, is required to help improve prognosis, and reduce the consequences of cancer-associated nutritional decline.
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              The Tumor Microenvironment in Esophageal Cancer

              Esophageal cancer is a deadly disease, ranking sixth among all cancers in mortality. Despite incremental advances in diagnostics and therapeutics, esophageal cancer still carries a poor prognosis, and thus there remains a need to elucidate the molecular mechanisms underlying this disease. There is accumulating evidence that a comprehensive understanding of the molecular composition of esophageal cancer requires attention to not only tumor cells but also the tumor microenvironment, which contains diverse cell populations, signaling factors, and structural molecules that interact with tumor cells and support all stages of tumorigenesis. In esophageal cancer, environmental exposures can trigger chronic inflammation, which leads to constitutive activation of pro-inflammatory signaling pathways that promote survival and proliferation. Anti-tumor immunity is attenuated by cell populations such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs), as well as immune checkpoints like programmed death-1 (PD-1). Other immune cells such as tumor-associated macrophages can have other pro-tumorigenic functions, including the induction of angiogenesis and tumor cell invasion. Cancer-associated fibroblasts secrete growth factors and alter the extracellular matrix (ECM) to create a tumor niche and enhance tumor cell migration and metastasis. Further study of how these TME components relate to the different stages of tumor progression in each esophageal cancer subtype will lead to development of novel and specific TME-targeting therapeutic strategies, which offer considerable potential especially in the setting of combination therapy.
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                Author and article information

                Contributors
                jianghao1223@hotmail.com , jianghao1223@163.com
                Journal
                Cancer Med
                Cancer Med
                10.1002/(ISSN)2045-7634
                CAM4
                Cancer Medicine
                John Wiley and Sons Inc. (Hoboken )
                2045-7634
                02 April 2018
                May 2018
                : 7
                : 5 ( doiID: 10.1002/cam4.2018.7.issue-5 )
                : 1837-1844
                Affiliations
                [ 1 ] Department of Radiation Oncology The First Affiliated Hospital of Bengbu Medical College No. 287, Chang Huai Road Bengbu 233000 China
                Author notes
                [*] [* ] Correspondence

                Hao Jiang, Department of Radiation Oncology, The First Affiliated Hospital of Bengbu Medical College, No. 287, Chang Huai Road, Bengbu 233000, China. Tel: +86 552 3086212; Fax: +86 552 3086212; E‐mails: jianghao1223@ 123456hotmail.com , jianghao1223@ 123456163.com

                [†]

                Both of the authors contributed equally to this work.

                Author information
                http://orcid.org/0000-0001-7200-5087
                Article
                CAM41456
                10.1002/cam4.1456
                5943545
                29608256
                75172520-870d-4c94-8577-b583d236f477
                © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 January 2018
                : 24 February 2018
                : 28 February 2018
                Page count
                Figures: 2, Tables: 4, Pages: 8, Words: 6206
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 31200633
                Funded by: Natural Science Foundation of Bengbu Medical College
                Award ID: BYKY1725ZD
                Categories
                Original Research
                Clinical Cancer Research
                Original Research
                Custom metadata
                2.0
                cam41456
                May 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.7.2 mode:remove_FC converted:09.05.2018

                Oncology & Radiotherapy
                concurrent chemoradiation,definitive radiotherapy,neutrophil–lymphocyte ratio,nutritional risk index,very elderly esophageal cancer

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