Imaging modalities for diagnosis and monitoring of cancer cachexia

Abstract

Cachexia, a multifactorial wasting syndrome, is highly prevalent among advanced-stage cancer patients. Unlike weight loss in healthy humans, the progressive loss of body weight in cancer cachexia primarily implicates lean body mass, caused by an aberrant metabolism and systemic inflammation. This may lead to disease aggravation, poorer quality of life, and increased mortality. Timely detection is, therefore, crucial, as is the careful monitoring of cancer progression, in an effort to improve management, facilitate individual treatment and minimize disease complications. A detailed analysis of body composition and tissue changes using imaging modalities—that is, computed tomography, magnetic resonance imaging, (18F) fluoro-2-deoxy-d-glucose (18FDG) PET and dual-energy X-ray absorptiometry—shows great premise for charting the course of cachexia. Quantitative and qualitative changes to adipose tissue, organs, and muscle compartments, particularly of the trunk and extremities, could present important biomarkers for phenotyping cachexia and determining its onset in patients. In this review, we present and compare the imaging techniques that have been used in the setting of cancer cachexia. Their individual limitations, drawbacks in the face of clinical routine care, and relevance in oncology are also discussed.

Primary Tumor Fluorine‐18 Fluorodeoxydglucose (18F‐FDG) Is Associated With Cancer-Associated Weight Loss in Non-Small Cell Lung Cancer (NSCLC) and Portends Worse Survival

“…This might be particularly relevant within the context of cancer-associated weight loss and cachexia, as escalated glucose consumption by tumors can distort systemic metabolic flux and suggest increasingly malignant genetic dysregulation through mechanisms such as the Warburg effect. Our research team previously demonstrated the relevance of 18 F-FDG uptake in incidence of significant pretreatment weight loss and survival for patients with gastroesophageal cancer (17). Prior studies have supported alternate uses of PET imaging for the detection of cancer cachexia (18), linking low hepatic uptake (19) and increased metabolically active brown adipose tissue uptake (20) of 18 F-FDG with the syndrome.…”

“…Our research team previously demonstrated the relevance of 18 F-FDG uptake in incidence of significant pretreatment weight loss and survival for patients with gastroesophageal cancer (17). Prior studies have supported alternate uses of PET imaging for the detection of cancer cachexia (18), linking low hepatic uptake (19) and increased metabolically active brown adipose tissue uptake (20) of 18 F-FDG with the syndrome.…”

“…PET is often performed with the intravenous administration of fluorine-18fluoro-2-deoxy-D-glucose ( 18 F-FDG), a positron emitting glucose molecule. 18 F-FDG accumulates in organs with high glucose utilization such as the brain, heart, and liver. Malignant cells demonstrate increased uptake of 18 F-FDG on PET due to overexpression of GLUT receptors and elevated intracellular levels of hexokinase, which generate increased rates of glycolysis (6,12,13).…”

“…18 F-FDG accumulates in organs with high glucose utilization such as the brain, heart, and liver. Malignant cells demonstrate increased uptake of 18 F-FDG on PET due to overexpression of GLUT receptors and elevated intracellular levels of hexokinase, which generate increased rates of glycolysis (6,12,13). Another contributing phenomenon is the Warburg effect, in which tumor cells preferentially undergo anaerobic glycolysis to produce ATP, regardless of being in nonhypoxic conditions (14).…”

“…The endpoint of these metabolic processes is fluorinated glucose trapped within the cell with characteristic increased activity on PET. The measure of 18 F-FDG uptake is commonly quantified using standardized uptake values (SUV), a measurement of tracer uptake in a lesion normalized to injected activity and volume of distribution (15,16). SUV should therefore function as a measure of tumor glycolytic capacity.…”