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      Understanding Cancer Cachexia and Its Implications in Upper Gastrointestinal Cancers

      review-article
      , BMedSci (Hons) MBChB MRCS (Ed) 1 , , , MBChB MRCGP DRCOG MD 2 , 3 , , BSc (Hons) MBBS MD FRCS (Ed) FRCP (Ed) FRSE 1 , , BSc (Hons) MBChB MD FRCS (Ed) MFSTEd 1
      Current Treatment Options in Oncology
      Springer US
      Oesophageal cancer, Gastric cancer, Oesophagogastric cancer, Upper gastrointestinal cancer, Cachexia, Catabolism, Muscle-wasting, Body composition, Weight loss

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          Opinion statement

          Considerable advances in the investigation and management of oesophagogastric cancer have occurred over the last few decades. While the historically dismal prognosis associated with these diseases has improved, outcomes remain very poor. Cancer cachexia is an often neglected, yet critical, factor for this patient group. There is a persuasive argument that a lack of assessment and treatment of cachexia has limited progress in oesophagogastric cancer care. In the curative setting, the stage of the host (based on factors such as body composition, function, and inflammatory status), alongside tumour stage, has the potential to influence treatment efficacy. Phenotypical features of cachexia may decrease the survival benefit of (peri-operative) chemoradiotherapy, immunotherapy, or surgical resection in patients with potentially curative malignancy. Most patients with oesophagogastric cancer unfortunately present with disease which is not amenable, or is unlikely to respond, to these treatments. In the palliative setting, host factors can similarly impair results from systemic anti-cancer therapies, cause adverse symptoms, and reduce quality of life. To optimise treatment pathways and enhance patient outcomes, we must utilise this information during clinical decision-making. As our understanding of the genesis of cancer cachexia improves and more therapeutic options, ranging from basic (e.g. exercise and nutrition) to targeted (e.g. anti-IL1 α and anti-GDF-15), become available, there can be grounds for optimism. Cachexia can change from a hitherto neglected condition to an integral part of the oesophagogastric cancer treatment pathway.

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          Most cited references83

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            Definition and classification of cancer cachexia: an international consensus.

            To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index [BMI] <20 kg/m(2)) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages--precachexia to cachexia to refractory cachexia. Severity can be classified according to degree of depletion of energy stores and body protein (BMI) in combination with degree of ongoing weight loss. Assessment for classification and clinical management should include the following domains: anorexia or reduced food intake, catabolic drive, muscle mass and strength, functional and psychosocial impairment. Consensus exists on a framework for the definition and classification of cancer cachexia. After validation, this should aid clinical trial design, development of practice guidelines, and, eventually, routine clinical management. Copyright © 2011 Elsevier Ltd. All rights reserved.
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              Perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomised, phase 2/3 trial

              Docetaxel-based chemotherapy is effective in metastatic gastric and gastro-oesophageal junction adenocarcinoma. This study reports on the safety and efficacy of the docetaxel-based triplet FLOT (fluorouracil plus leucovorin, oxaliplatin and docetaxel) as a perioperative therapy for patients with locally advanced, resectable tumours.
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                Author and article information

                Contributors
                leorbrown@doctors.org.uk
                barry.laird@ed.ac.uk
                s.wigmore@ed.ac.uk
                Richard.Skipworth@nhslothian.scot.nhs.uk
                Journal
                Curr Treat Options Oncol
                Curr Treat Options Oncol
                Current Treatment Options in Oncology
                Springer US (New York )
                1527-2729
                1534-6277
                21 October 2022
                21 October 2022
                2022
                : 23
                : 12
                : 1732-1747
                Affiliations
                [1 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Clinical Surgery, , University of Edinburgh, Royal Infirmary of Edinburgh, ; Edinburgh, Scotland EH16 4SA UK
                [2 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Institute of Genetics and Cancer, , University of Edinburgh, Western General Hospital, ; Edinburgh, Scotland EH4 2XU UK
                [3 ]St Columba’s Hospice, Edinburgh, Scotland EH5 3RW UK
                Author information
                http://orcid.org/0000-0001-6181-7020
                Article
                1028
                10.1007/s11864-022-01028-1
                9768000
                36269458
                17b47b7a-9516-46cb-ba56-950528c7a797
                © The Author(s) 2022

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 9 October 2022
                Categories
                Upper Gastrointestinal Cancers (JD Berlin, Section Editor)
                Custom metadata
                © Springer Science+Business Media, LLC, part of Springer Nature 2022

                Oncology & Radiotherapy
                oesophageal cancer,gastric cancer,oesophagogastric cancer,upper gastrointestinal cancer,cachexia,catabolism,muscle-wasting,body composition,weight loss

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