Cancer cachexia: A systematic literature review of items and domains associated with involuntary weight loss in cancer☆,☆☆,★,★★
Introduction
A majority of patients with advanced cancer experience involuntary loss of weight [1]. A main cause for involuntary weight loss (WL) is cancer cachexia; a metabolic, paraneoplastic syndrome, often accompanied by anorexia, which leads to decreased physical function and psychological distress, affecting also patients’ loved ones [3]. The causes of cancer cachexia are complex and are triggered by tumor products and pro-inflammatory cytokines [4].
The historic, common definition of cancer cachexia is limited to WL and anorexia [5]. Although it has face-validity as an approach to screening, this minimalistic approach seems inadequate to guide clinical care decisions [6].
A generic definition for cachexia/wasting disease associated with any form of chronic illness was recently composed in a consensus meeting [8], and the SCRINIO Working Group [1], [96] recently proposed a cancer cachexia classification after examining a database of 1307 cancer outpatients.
The European Palliative Care Research Collaborative, funded by the European Union's 6th framework in 2006 [7] is developing classification systems for pain, depression and cachexia in patients with advanced cancer. Candidate items for cachexia classification include subjective assessments, blood tests, images, and other measurements [8].
Cancer cachexia is invariably described as being multifactorial, with many axes of complexity. Weight loss may be composed of lean or adipose tissues in different degree, with varying functional consequences. Weight loss is understood to be driven in a varying degree by low food intake, which in turn may be the result of a wide variety of symptoms directly (e.g., anorexia, dysphagia, dysgeusia) or indirectly (e.g., pain, fatigue) limiting oral intake. A variety of metabolic and endocrine changes and activation of catabolic pathways, accounts for some of the weight loss, which is typically greater than would be expected for the prevailing level of intake [9], [10], [11], [12], [13], [14], [15]. Functional deficits associated with cachexia may be physical, immune, metabolic or psychosocial. Cancer cachexia definition, classification and diagnostic criteria must integrate all of these facets in a relevant way, and this remains a considerable challenge. A consensus of the various attempts to define cachexia has recently been published [102].
Our aim was to perform a systematic literature review using bibliographic databases to identify relevant articles for critical evaluation of items associated with involuntary WL in cancer patients.
Section snippets
Methods
For the purpose of this review and reflecting its current broad definition, cancer cachexia was defined as involuntary WL.
Results
Sixty-five cross-sectional and six longitudinal studies with overall 6325 patients (40–50% gastrointestinal-, 10–20% lung cancer) were retrieved (Fig. 1). WL data were variously reported as percentages lost (5% [n = 12 papers], 10% [n = 20], or specific percentages [n = 29]) or absolute quantity lost in kilograms (n = 10) compared with either pre-illness weight [n = 33] or during a recent time period (6 months [n = 18], 3 months [n = 4], or not specified [n = 16]).
Discussion
This is the first systematic literature review of the main items associated with involuntary loss of weight in cancer. No single item could consistently distinguish cancer patients with or without WL or having various degrees of WL.
The definitions for the amount and the duration of WL that was sufficient to characterise cachexia were very heterogeneous, mirroring the historic lack of a consensus definition. New definitions for cancer cachexia [102] will improve direct comparability of future
Conflict of interest
The authors report no conflict of interest.
Reviewers
Prof. Alessandro Laviano, Sapienza University, Department of Clinical Medicine, viale dell’Università 37, I-00185 Rome, Italy.
Dr. Nathalie Jacquelin-Ravel, Clinique de Genolier, 1 route du Muids, CH-1272 Genolier, Switzerland.
Acknowledgments
We thank Daniel Kauffmann, Librarian, Jochen Walker, Medical Informatics, and Nicole Schenk, Project Management, in the Cantonal Hospital St.Gallen. Several collaborators participating in the EPCRC provided support during the process of this manuscript, namely the Trondheim Group and the Aachen group with Lukas Radbruch and Peter Trottenberg.
Special thanks to the participants of the cachexia track in the Lofoten conference 2008 (Frieda Barak, Vickie E. Baracos, David Blum, James Cleary, Ken
David Blum obtained his medical degree from the University of Zürich (2002). He received the Swiss Confederation Diploma (FMH) Internal Medicine and is currently working as resident doctor and research fellow at Oncological Palliative Medicine, Oncology/Hematology, Department Internal Medicine and Palliative Center, Kantonsspital St.Gallen. He is member Swiss Society of Palliative Care (SSPC) and European Society of Medical Oncology (ESMO) His research interests include cancer cachexia,
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David Blum obtained his medical degree from the University of Zürich (2002). He received the Swiss Confederation Diploma (FMH) Internal Medicine and is currently working as resident doctor and research fellow at Oncological Palliative Medicine, Oncology/Hematology, Department Internal Medicine and Palliative Center, Kantonsspital St.Gallen. He is member Swiss Society of Palliative Care (SSPC) and European Society of Medical Oncology (ESMO) His research interests include cancer cachexia, physical activity and end-of-life care.
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The authors are part of the European Palliative Care Research Collaborative, which is funded by the European Commission's Sixth Framework Programme (contract no. LSHC-CT-2006-037777) with the overall aim to improve treatment of pain, depression and fatigue through translation research.
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Core scientific group/work package leaders: Stein Kaasa (project coordinator), Frank Skorpen, Marianne Jensen Hjermstad, and Jon Håvard Loge, Norwegian University of Science and Technology (NTNU); Geoffrey Hanks, University of Bristol; Augusto Caraceni and Franco De Conno, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan; Irene Higginson, King's College London; Florian Strasser, Cantonal Hospital St. Gallen; Lukas Radbruch, RWTH Aachen University; Kenneth Fearon, University of Edinburgh; Hellmut Samonigg, Medical University of Graz; Ketil Bø, Trollhetta AS, Norway; Irene Rech-Weichselbraun, Bender MedSystems GmbH, Austria; Odd Erik Gundersen, VerdandeTechnology AS, Norway. Scientific advisory group: Neil Aaronson, The Netherlands Cancer Institute; Vickie Baracos and Robin Fainsinger, University of Alberta; Patrick C. Stone, St. George's University of London; Mari Lloyd-Williams, University of Liverpool. Project management: Stein Kaasa, Ola Dale, and Dagny F. Haugen, NTNU.
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Research support: European Palliative Care Research Collaborative (EPCRC), an EU framework 6 funded consortium. Eagle foundation, Switzerland.
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Originality of the work and presentation of study: This report represents original work designed, performed, analyzed, and reported by the authors. Aspects of this work were presented at the 5th Research Forum of the European Association of Palliative Care, 2008, Trondheim as oral presentation: Florian Strasser, David Blum, Aurelius Omlin, Jochen Walker, Ken Fearon. A novel Cachexia Classification for Palliative Cancer Care: Synthesis of systematic literature reviews and nominal experts’ focus group. An EPCRC-project. Palliative Medicine 2008;22:410 (Abstract 36) at the 11th Congress of the European Association of Palliative Care, 2009, Vienna, as Poster: Blum D, Omlin A, Baracos V, Skeidsvoll T, Tan B, Hess J, Fearon K, Strasser F. Inflammation and nutritional intake: Are they really needed to classify cancer cachexia? A systematic literature review. Eur J Pall Care 2009;130 (PE 1.F450) and at the ECCO 15 – ESMO 34 Congress 2009 in Berlin as invited lecture in the SYMPTOM SCIENCE Scientific Symposium (23.9.09; 14:45-16:45; Symptom management: from molecular biology to bedside including pain and cachexia): Strasser F, Blum D, Oberholzer R, Linder S, Fearon K, Radbruch L, Kaasa S. Treatment of cachexia—a preventive or symptomatic approach?.