University of Alberta
Presentation Abstract
Body Composition and its Evolution in Advanced Stage Cancer: Tumor and Systemic Treatment-Related Side Effects
Computed tomography images acquired during routine cancer care provide an opportunity to determine body composition with accuracy and precision. Quantification of skeletal muscle is of interest owing to its association with diverse clinical outcomes. Rigorous attention to measurement precision is required to detect changes in body composition over time, to discriminate clinical–biological change from measurement error. Reduced muscle mass at time of diagnosis of advanced–metastatic disease is prognostic of survival. Further wasting of muscle mass ensues over time during systemic therapy, independent of tumor response, with higher intensity of muscle loss associated with poorer prognosis compared with stability/gain of muscle mass over time. A vicious cycle is apparent involving depletion of the muscle mass and toxicity of systemic therapy, wherein individuals reduced muscle mass has an increased risk of treatment toxicity and further reduction of muscle mass is a side effect of systemic therapy. The biology of these effects is only partly understood, however it is suggested that a) patients with a relatively low skeletal muscle mass relative to their body surface area experience higher dose-intensity due to decreased volume of distribution, clearance or both, and b) specific cytotoxic and targeted chemotherapies directly elicit proteolysis (atrophy gene transcriptional program) as well as reduced protein anabolism at the tissue level. The summative effects of tumor progression and multiple lines of therapy result in profound wasting of both muscle and adipose tissue over the disease course.
About Dr. Baracos
Dr. Baracos is a Professor and Alberta Cancer Foundation Chair in Palliative Care Medicine in the Department of Oncology at the University of Alberta, Canada. Dr. Baracos received her B.Sc. (1977) from the University of Alberta, Canada, Ph.D. in applied biochemistry (1981) from Nottingham University, and completed postdoctoral training in physiology (1981-1984) at Harvard Medical School. The long term focus of Dr. Baracos’ career has been the pathophysiology of skeletal muscle atrophy in an effort that encompasses fundamental and translational research, a clinical research agenda, and an international network of strategic collaboration. Cancer cachexia, a debilitating condition characterized by profound atrophy of skeletal muscle has been her main focus since 2003. Some key publications include Baracos VE, et al. Cancer-associated cachexia. Nature Reviews Disease Primers. 2018; 4:17105; Martin L, et al. Diagnostic criteria for the classification of cancer-associated weight loss. Journal of Clinical Oncology. 2015;33(1):90-9; and Fearon K, et al. Definition and classification of cancer cachexia: an international consensus. The Lancet Oncology. 2011;12(5):489-95. Dr. Baracos developed the use of clinical computed tomography to detect and precisely measure the muscle loss, which is an integral part of cachexia. Muscle loss is strongly associated with severe chemotherapy toxicity, complications of surgery, and mortality in patients with different cancers. Her work is supported by the Canadian Institutes of Health Research and the Alberta Cancer Foundation.
Dr. Baracos disclosed the following conflicts of interest for this workshop: consulting for Nestle Health Sciences, Pfizer Inc., and Baxter Healthcare.