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Nutrition Assessment in Medical and Surgical Oncology
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- Author / Creator
- Martin, Lisa
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Introduction:Cancer-associated cachexia is defined as a multifactorial syndrome characterized by loss of body weight with specific losses of skeletal muscle and adipose tissue. Cachexia is driven by a variable combination of reduced food intake (FI) and distinct tumor-associated metabolic changes, including elevated energy expenditure, excess catabolism, and inflammation. Patients with cachexia experience weakness, fatigue, loss of independence, poor treatment tolerance, and death. Cachexia may be present at the time of cancer diagnosis or develop and worsen with cancer treatment and disease progression. There are no widely agreed upon diagnostic criteria, which have hindered diagnosis, clinical management and development of effective treatments. An International Consensus Framework for the Definition and Classification of Cancer Cachexia made recommendations for development of diagnostic criteria, suggesting ‘definitive cutoffs for variables (e.g. weight loss, low muscle mass) could be determined from large contemporary datasets by determining the values that relate optimally to meaningful patient-centered outcomes, such as loss of function or decreased survival’ The objective of my thesis was to advance development of diagnostic criteria for cancer cachexia in at risk patient populations from two cancer treatment settings, medical and surgical oncology. Methods:Large contemporary data sets were lacking to study patients with cancer cachexia. International research partners contributed data from clinical cachexia research studies to create aggregated data sets for secondary data analysis. Data included candidate diagnostic criteria (e.g. body mass index (BMI), weight loss (WL), computed tomography (CT)-defined body composition, FI, and C-reactive protein (CRP, as a marker of inflammation), covariates (e.g. cancer type, stage, surgical approach, age, sex, performance status), and patient-centered outcomes (e.g. overall survival (OS), length of hospital stay (LOS)). In medical oncology, the prognostic impact of candidate diagnostic criteria (WL, BMI, FI, and CRP) on OS was evaluated with Kaplan Meier and multivariable Cox proportional hazard models; FI and CRP were evaluated as etiological criteria for WL with multivariable multinomial logistic regression (MLR) models. In the surgical setting, the prognostic impact of candidate diagnostic criteria (WL, FI, and CT-defined body composition) on LOS, postoperative complications, and 30-day hospital readmission were evaluated with multivariable logistic (LR) and negative binomial (NMR) regression models.Results:Large aggregated data sets were created to study patients from medical (N=18,173 patients) and surgical (N=5,739) oncology settings. Three studies were conducted with data from medical oncology. Study 1 demonstrated that increased %WL and decreased BMI independently predicted OS. A grading system combining %WL and BMI was developed based on OS (Grade 0 (longest OS) to 4 (shortest OS)), and was subsequently validated. In studies 2 & 3, FI and CRP were evaluated as etiological criteria for WL. Common values, based on relative risk of weight loss, were determined across the 3 most frequently used clinical measurement scales for FI, which were combined (normal, moderately or severely reduced) and evaluated. Reduced FI significantly associated with increasingly severe WL. The relationship between CRP and WL was also evaluated; CRP values (<10, 10-43, and ≥43 mg/L) associated with distinct degrees of WL were defined. In multivariable MLR both CRP and FI significantly associated with increasingly severe WL, and the combination of WL, FI, and CRP identified patients with significantly different OS.Two studies were conducted with data from surgical oncology. In the first study, nutrition risk (based on WL and reduced FI) was identified as an independent predictor of low compliance to a standardized multi-modal care pathway, which had a significant negative impact on postoperative complications and LOS. In the second study, age- and sex-specific preoperative body composition profiles were defined based on combinations of CT-defined low skeletal muscle, low skeletal muscle radiation attenuation, and high visceral fat. Multidimensional body composition profiles were at significant risk of longer LOS and increased 30-day hospital readmission.Conclusions:Candidate diagnostic available for aggregation were heterogeneous, and represented with variable frequency. Alterations in metabolism were only represented by a single criterion, CRP. Identifying common values between different measurement scales for FI facilitated data aggregation. Evaluation of aggregated data identified WL, BMI, FI, CRP, and CT-defined body composition as candidate diagnostic criteria for cancer cachexia that identified patients at risk for poor outcomes in different care settings. These criteria are a key first step toward development of definitive diagnostic criteria, and require prospective validation.
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- Graduation date
- Spring 2019
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- Type of Item
- Thesis
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- Degree
- Doctor of Philosophy
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- License
- Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.