Investigating the biological and clinical characterisation of sarcopenia and anorexia in patients with cancer

Abstract

Advanced oesphagogastric (OG) tract cancers are commonly associated with appetite loss (anorexia), muscle loss (sarcopenia) and malnutrition. Outcomes for advanced disease are poor with average survival under 1 year and anorexia, sarcopenia and malnutrition are individually associated with poor prognosis. Sarcopenia is common in frail patients but its correlation with frailty scores is not fully understood. Furthermore, the underlying pathophysiology of anorexia and sarcopenia are incompletely understood. The aim of this work was to deeply characterise the prevalence and patterns of anorexia and sarcopenia in patients with advanced OG cancers and investigate a potential mechanism for anorexia through an assessment of gut hormones. Anorexia is highly prevalent (63%) and trends towards an association with poorer survival but not treatment toxicity. Weight loss was significant at baseline and was associated with survival at more severe levels. Levels of the anorexigenic gut hormone PYY were raised in patients with cancer anorexia compared to those with no anorexia and this may suggest a potential mechanism for this symptom. Insulin, GIP and GLP-1 responses were blunted in anorexic patients, but this did not produce a raised glucose level and the cause for this is unclear. Sarcopenia was also highly prevalent, but did not correlate with frailty scores, survival, or treatment toxicity. A scoping review of medications trialled for sarcopenia identified positive results for androgens, growth hormone and newer agents targeting muscle catabolism. However, gains are frequently small and not associated with an increase in function. This raises the question of what would be considered a meaningful outcome for patients with advanced cancer. This work provides a foundation for extended research into nutritional symptoms in patients with advanced OG cancers. Careful patient characterisation is important in researching these patients to allow for individualised treatment plans.

Date of Award	1 Aug 2023
Original language	English
Awarding Institution	The University of Manchester
Supervisor	James Weaver (Supervisor), John Mclaughlin (Supervisor) & Abdul Mansoor (Supervisor)