title: An investigation of CT derived body composition, host nutritional status, systemic inflammation and clinical outcomes in patients with common solid tumours
Creators: name: Abbass, Tanvir
Publisher: name: University of Glasgow
Year: 2023

description: Colorectal and lung cancers are common solid tumours in Western populations. While colorectal cancer presents largely at an early, operable stage, lung cancer presents largely at an advanced inoperable stage. Although tumour related characteristics are important part of cancer staging, host factors are increasingly recognised to impact on oncological treatment and clinical outcomes. Recently CT-derived body composition treatment has become available to supplement other host factors such as malnutrition risk, frailty, performance status and systemic inflammation. Importantly, these host characteristics are potentially modifiable. The aim of the present thesis was to examine the relationships between CT-derived body composition, host nutritional status, systemic inflammation and clinical outcomes in patients with common solid tumours.

Chapter 1, critically reviewed the importance of CT derived body composition and the barriers to universal application of this modality for improving the staging and treatment of common solid tumours. Specifically, computed tomography (CT) based body composition analysis methods were critically reviewed and further directions to achieve body composition in routine clinical practice were highlighted. Moreover, the relationship between imaging based body composition and systemic inflammation in patients with common solid tumours was systematically reviewed. The systemic inflammatory response was directly associated with low skeletal muscle index (SMI) and low skeletal muscle density (SMD). 

Chapter 2, examined the relationship between psoas and all other skeletal muscles at L3 level with regards to clinical outcomes in patients with operable CRC. Critical analysis of value of L3 skeletal muscle and psoas muscle area in 1002 patients with operable CRC was performed. Both psoas and whole skeletal muscles at L3 were moderately correlated and both had prognostic value in terms of clinical outcomes including length of hospital stay and overall survival. However, only SMI had independent prognostic value in patients with operable CRC. 

Chapter 3, examined the relationship between MUST, systemic inflammation, body composition and clinical outcomes in patients with operable colorectal cancer. In patients with mild and moderate / high nutrition risk, systemic inflammation was associated with low SMI, greater length of stay and poorer overall survival. The MUST and mGPS has complementary prognostic value and may form the basis of routine disease related malnutrition assessment in patients with primary operable CRC. It was also proposed that cachexia may be defined as disease related malnutrition with systemic inflammation. The management directions for these patients should include reducing catabolism and improving anabolic response by addressing malnutrition, SIR, muscle mass and function. 

Chapter 4, examined the relationship between MUST, systemic inflammation, body composition and survival in patients with advanced lung cancer. Similar relationships were seen as in patients with CRC. The patients who were malnourished, frail, inflamed and had low SMI had poor survival as compared to patients who were not. This study suggested that combination of MUST, ECOG and mGPS provides a framework to identify the groups of patients who will benefit from aggressive oncological treatment or referral to the palliative care team. Moreover, new GLIM criteria captures components of MUST and the mGPS, highlighting the fact that host characteristics including malnutrition, systemic inflammation are important characteristics in decision making process to decide targeted treatment. 

Chapter 5, examined the longitudinal relationship between MUST, SIR and body composition in patients with advanced lung cancer. Over approximately, 3 months longitudinal study period, there was increase in malnutrition, worsened performance status, increase in SIR (mGPS and NLR), decrease in subcutaneous, visceral adiposity, SMI and SMD. Longitudinal MUST, ECOG, mGPS and NLR were associated with overall survival. No measurement of body composition was associated with overall survival. The loss of muscle was associated with SIR. The loss of body mass should be considered in the context of malnutrition risk, performance status and systemic inflammation. 

Chapter 6, examined the comparative analysis of CT derived measures of body composition across two solid tumours (CRC and LC). The comparison was performed in view of significant differences in two cohorts. CRC cohort included patients with operable disease whereas LC included patients with advanced disease undergoing radiotherapy. CRC is less inflammatory cancer and patients maintain body composition over longitudinal study period, whereas LC is pro inflammatory and patients lose more fat and muscle mass. CRC involves gastrointestinal tract and LC did not. The percentage of obesity and low SMI were similar between two cohorts despite large differences in clinicopathological characteristics. It was also, highlighted in this comparison that CT derived body composition although prognostic, is a result of patient constitution rather than tumour itself. The systemic inflammatory response as evidenced by mGPS in this study can be considered as important therapeutic target and loss of muscle mass in patients with advanced cancer is related to systemic inflammatory response. 

Chapter 7, examined advanced lung cancer patients who had PET-CT pre-treatment and its relationship to MUST, systemic inflammation and metabolic uptake were examined. There was direct relationship between mGPS and FDG uptake. MUST, mGPS and FDG uptake were associated with overall survival. SIR was associated with loss of muscle and frailty. The combination of clinicopathological (MUST, ECOG, frailty) and radiological parameters (FDG uptake) provide comprehensive host assessment to guide targeted treatment. These observations are relevant in pre-treatment as well as when measured longitudinally at 3 months interval in advanced lung cancer cohort. The patients who continue to deteriorate despite radiotherapy with increased inflammation and loss of muscle mass, should be directed to the best palliative care. 

Chapter 8 Conclusions: Host and tumour characteristics are important for best possible outcome in treating a patient with cancer. Staging the host as well as staging the tumour is an important concept for decision making and to provide best targeted therapy. Important host characteristics include MUST, ECOG, SIR and CT derive body composition. These characteristics when applied to the patient treatment can provide comprehensive phenotype to decide the treatment or palliation course. This thesis examined these characteristics across two solid tumour types of diverse phenotypes. Inflammation and body composition were related to each other. The longitudinal studies as well as comparative analysis between two cancers provides a significant insight to determine future directions for targeted treatment and palliation. It was observed that patients with advanced lung cancer get more malnourished, more inflamed, more muscle loss and have worse overall survival when compared to operable CRC.