A prospective study examining cachexia predictors in patients with incurable cancer

Vagnildhaug, Ola Magne; Brunelli, Cinzia; Hjermstad, Marianne J.; Strasser, Florian; Baracos, Vickie; Wilcock, Andrew; Nabal, Maria; Kaasa, Stein; Laird, Barry; Solheim, Tora S.

Abstract

© 2019 The Author(s). Background: Early intervention against cachexia necessitates a predictive model. The aims of this study were to identify predictors of cachexia development and to create and evaluate accuracy of a predictive model based on these predictors. Methods: A secondary analysis of a prospective, observational, multicentre study was conducted. Patients, who attended a palliative care programme, had incurable cancer and did not have cachexia at baseline, were amenable to the analysis. Cachexia was defined as weight loss (WL) > 5% (6 months) or WL > 2% and body mass index< 20 kg/m2. Clinical and demographic markers were evaluated as possible predictors with Cox analysis. A classification and regression tree analysis was used to create a model based on optimal combinations and cut-offs of significant predictors for cachexia development, and accuracy was evaluated with a calibration plot, Harrell's c-statistic and receiver operating characteristic curve analysis. Results: Six-hundred-twenty-eight patients were included in the analysis. Median age was 65 years (IQR 17), 359(57%) were female and median Karnofsky performance status was 70(IQR 10). Median follow-up was 109 days (IQR 108), and 159 (25%) patients developed cachexia. Initial WL, cancer type, appetite and chronic obstructive pulmonary disease were significant predictors (p ≤ 0.04). A five-level model was created with each level carrying an increasing risk of cachexia development. For Risk-level 1-patients (WL < 3%, breast or hematologic cancer and no or little appetite loss), median time to cachexia development was not reached, while Risk-level 5-patients (WL 3-5%) had a median time to cachexia development of 51 days. Accuracy of cachexia predictions at 3 months was 76%. Conclusion: Important predictors of cachexia have been identified and used to construct a predictive model of cancer cachexia. Trial registration: ClinicalTrials.gov Identifier: NCT01362816.

Citation

Vagnildhaug, O. M., Brunelli, C., Hjermstad, M. J., Strasser, F., Baracos, V., Wilcock, A., …Solheim, T. S. (2019). A prospective study examining cachexia predictors in patients with incurable cancer. BMC Palliative Care, 18, Article 46. https://doi.org/10.1186/s12904-019-0429-2

• Journal Article Type: Article
• Acceptance Date: May 20, 2019
• Online Publication Date: Jun 4, 2019
• Publication Date: Jun 4, 2019
• Deposit Date: May 24, 2019
• Publicly Available Date: May 24, 2019
• Journal: BMC Palliative Care
• Electronic ISSN: 1472-684X
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 18
• Article Number: 46
• DOI: https://doi.org/10.1186/s12904-019-0429-2
• Keywords: Cachexia; Pre-cachexia; Weight loss; Cancer; Palliative care
• Public URL: https://nottingham-repository.worktribe.com/output/2088494
• Publisher URL: https://bmcpalliatcare.biomedcentral.com/articles/10.1186/s12904-019-0429-2
• Additional Information: Received: 31 August 2018; Accepted: 20 May 2019; First Online: 4 June 2019; : The study was conducted in keeping with the Helsinki declaration and its amendments. All patients had to provide written informed consent. The protocol was approved by the Regional Committee for Medical and Health Research Ethics in Central Norway (reference number 2010/2945) corresponding to the location of the Project Management Office. In addition, the ethics committees/institutional review boards of following centers gave ethical approval for the study: Southern Adelaide Palliative Services, Adelaide, South Australia (AU), University Hospital, Ghent (BE), Comprehensive Cancer Centre, Vratsa (BG), Cross Cancer Institute, Northern Alberta (CA), The Edmonton Zone Palliative Care Program, Alberta (CA), Cantonal Hospital, St. Gallen (CH), Kantonsspital Graubünden, Chur (CH), Rigshospitalet, Copenhagen (DK), Bispebjerg Hospital, Copenhagen (DK), Hospital Universitario Arnau de Vilanova, Lleida (ES), Clínica Universidad de Navarra, Pamplona (ES), Hospital Centro de Cuidados Laguna, Madrid (ES), Institut Catala D’Oncologia, Barcelona (ES), Cancer Prevention Centre (CPC) Tblisi (GE), Fondazione IRCCS Istituto Nazionale dei Tumori, Milan (IT), Hospital of Piacenza, Piacenza (IT), Hospice Villa Speranza, Rome (IT), Istituti Clinici di Perfezionamento Hospital, Milan (IT), U.O. Complessa Cure Palliative e Terapia del Dolore Istituti Clinici di Perfezionamento, Milan (IT), University of L’Aquila, L’Aquila (IT), Arcispedale Santa Maria Nuova Reggio Emilia (IT), St. Olavs University Hospital, Trondheim (NO), Oslo University Hospital, Oslo (NO), Haraldsplass Deaconess Hospital, Bergen (NO), Øya Community Hospital, Trondheim (NO), Instituto Português de Oncologia de Lisboa Francisco Gentil, EPE, Lisbon (PT), St Gemmas Hospice, Leeds (UK), West Lothian Community Specialist Palliative Care Team, Edinburgh (UK), Nottingham University Hospitals, Nottingham (UK), Marie Curie Cancer Care Glasgow Hospice, Glasgow (UK).; : Not applicable.; : BL has received honoraria from Helsinn.FS has had punctual advisorships (boards, expert meetings) for Danone, Grünenthal, Helsinn, ISIS Global, Mundipharma, Novartis, Novelpharm, Obexia, Ono Pharmaceutical, Psioxus Therapeutics, PrIME Oncology, Sunstone Captial, Vifor. On behalf of his institution, he has received unrestricted industry grants for clinical research from Celgene, Fresenius and Helsinn. He has participated in a clinical cachexia trial lead by Novartis.OMV, CB, MJH, VEB, AW, MN, SK and TSS declare that they have no competing interest.
• Contract Date: May 24, 2019