Investigating the impact of body composition and nutritional intervention strategies in pancreatic cancer

Abstract

Introduction: Pancreatic adenocarcinoma (PDAC), while often described a rare or neglected cancer, is the fourth cause of cancer-related mortality in the US and Europe. Unintentional weight loss is a prominent feature of PDAC; over 80% of patients report weight loss at the time of their diagnosis. Persistent weight loss during treatment has been shown to be an adverse prognostic factor impacting both overall survival and patient-reported quality of life. Aim: The aims of this thesis were to investigate the prevalence and impact of sarcopenia or low muscle mass in patients with pancreatic cancer, and to explore the feasibility of a multi-modal intervention (designed to address weight and muscle loss) for patients undergoing neoadjuvant chemotherapy. Methods: Four interrelated studies were designed. A systematic review and meta-analysis were conducted to investigate the prevalence of sarcopenia in patients with resectable and/or borderline resectable pancreatic cancer. Following on from this, two retrospective cohort studies were designed using CT-based body composition analysis. The first study looked at the impact of sarcopenia on post-operative morbidity and mortality, while the second study characterised body composition change experienced by patients who received neoadjuvant chemotherapy. Lastly a prospective multi-modal nutritional intervention study was designed and evaluated in patients undergoing neoadjuvant chemotherapy Results: The systematic review and meta- analysis determined that 40% of patients with pancreatic cancer had low muscle mass at diagnosis, but heterogeneity was significant, limiting the ability to evaluate the impact it had on outcome Examination of the surgical cohort revealed that half of patients had sarcopenia and low /or muscle attenuation prior to surgery. Both factors impacted overall survival, while low muscle attenuation was associated with an increased risk of major post-operative morbidity. Sarcopenia and low muscle attenuation were equally prevalent among patients undergoing neoadjuvant chemotherapy. Low muscle attenuation at diagnosis, and muscle loss during chemotherapy, were independently associated with increased mortality risk. A multi-modal nutritional intervention was designed, comprising a fish-oil enriched supplement, pancreatic enzyme replacement therapy, individualised exercise advice, and intensive dietary counselling. Twenty patients enrolled in the 12-week study, and the majority found that the intervention was feasible as designed. Most patients demonstrated weight gain and functional improvements, highlighting anabolic potential exists in this patient group. Conclusion: These results highlight the significance of body composition in pancreatic cancer, and suggest intensive nutritional interventions, delivered concurrently to chemotherapy, can improve nutritional status and functional assessment parameters.