Nutrition challenges of cancer cachexia

Abstract

Cancer cachexia, or progressive weight loss, often despite adequate nutrition contributes greatly to cancer morbidity and mortality. Cachexia is metabolically distinct from starvation or protein malnutrition, although many patients with cancer and cachexia exhibit lowered appetite and food consumption. Tumors affect neural mechanisms that regulate appetite and energy expenditure, while promoting wasting of peripheral tissues via catabolism of cardiac and skeletal muscle, adipose, and bone.These multimodal actions of tumors on the host suggest a need for multimodal interventions. However, multiple recent consensus guidelines for management of cancer cachexia differ in treatment recommendations, highlighting the lack of effective, available therapies. Challenges to defining appropriate nutrition or other interventions for cancer cachexia include lack of consensus on definitions, low strength of evidence from clinical trials, and a scarcity of robust, rigorous, and mechanistic studies. However, efforts to diagnose, stage, and monitor cachexia are increasing along with clinical trial activity. Furthermore, preclinical models for cancer cachexia are growing more sophisticated, encompassing a greater number of tumor types in organ-appropriate contexts and for metastatic disease to model the clinical condition more accurately.It is expected that continued growth, investment, and coordination of research in this topic will ultimately yield robust biomarkers, clinically useful classification and staging algorithms, targetable pathways, pivotal clinical trials, and ultimately, cures. Here, we provide an overview of the clinical and scientific knowledge and its limitations around cancer cachexia.

Addressing unmet needs for people with cancer cachexia: recommendations from a multistakeholder workshop

“…Furthermore, with no validated cachexia screening tool readily available for clinicians in oncology care and a lack of consistent malnutrition screening, there are significant gaps in detection and management of the syndrome for many patients. 16 Among the cachexia academic community, there is significant enthusiasm for expanding awareness about cancer cachexia. Extending knowledge to primary care, community oncologists, patients, caregivers, and advocates is key to supporting the development of novel therapies, integration of supportive care, and implementation of care pathways that can successfully address the aspects of cancer cachexia most meaningful to the patient experience.…”

“…It is further characterized by dysregulation of host metabolic processes at the cellular and molecular level, including mitochondrial dysfunction, glucose dysmetabolism, and unbalanced lipolysis and proteolysis 14,15 . While it is unlikely that a single agent will treat all aspects of this syndrome, recent cachexia research has identified specific biological, endocrine, and immune mechanisms that precipitate loss of body weight, skeletal muscle, appetite, and physical function 16 . For example, factors produced by the tumour and by the host, including inflammatory cytokines, exosomes, small molecules, and microRNAs, signal on distant tissues to suppress food intake and induce catabolism of fat and muscle.…”

“…Clinicians noted gaps in training about cachexia and its clinical management, leading many medical oncologists to miss the diagnosis, recognizing cachexia only when people have become profoundly emaciated and weak. Furthermore, with no validated cachexia screening tool readily available for clinicians in oncology care and a lack of consistent malnutrition screening, there are significant gaps in detection and management of the syndrome for many patients 16 …”

“…These include a lack of biomarkers to prognosticate, diagnose, stage, and monitor cachexia, heterogeneity in patient selection, bias against anti‐cachexia trials in favour of anti‐tumour trials, lack of appropriate infrastructure, and absence of clarity regarding meaningful clinical endpoints from the regulatory agencies. The relatively low research activity in cachexia relative to cancer overall was also cited as a potential barrier to identifying novel targets for therapy 16 . Recommendations emerging from this discussion included the refinement of diagnostic criteria, development of biomarkers, organization of a cachexia‐specific clinical trials consortium, engagement of regulators to facilitate robust trial designs, and continued prioritization of cachexia research by funding agencies.…”

“… 14 , 15 While it is unlikely that a single agent will treat all aspects of this syndrome, recent cachexia research has identified specific biological, endocrine, and immune mechanisms that precipitate loss of body weight, skeletal muscle, appetite, and physical function. 16 For example, factors produced by the tumour and by the host, including inflammatory cytokines, exosomes, small molecules, and microRNAs, signal on distant tissues to suppress food intake and induce catabolism of fat and muscle. Furthermore, comorbidities including depression, anxiety, frailty, hypogonadism, uncontrolled pain, and altered gastrointestinal function may exacerbate the weight loss and functional decline seen in these patients.…”