FP1.1 - The relationship between tumour necrosis, the tumour microenvironment, systemic inflammation, body composition and survival in patients with operable colon cancer. Does tumour necrosis drive systemic inflammation and cachexia?

Abstract Introduction The prognostic value of the systemic inflammatory response and its incorporation into the definition of cancer cachexia (GLIM) is now established. However, the basis of the relationship between the tumour, its environment and the systemic inflammatory response is not clear. The aim of the present study is to examine this hypothesis in greater detail. Methods A total of 473 patients were included. Host and tumour characteristics were assessed including tumour cell signaling pathways, CT derived body composition and systemic inflammation (as assessed by SIG). Categorical variables were analysed using χ2 test for linear-by-linear association, or χ2 test for 2 by 2 tables. Survival analysis was carried out using univariate Cox regression. Results Tumour necrosis was associated with age (p<0.01), tumour location (p<0.01), T-stage (p<0.001), margin involvement (p<0.05), SIG (p<0.001), SMI (Martin, p<0.01), SMI (Dolan, p<0.01), SMD (Dolan, p<0.05) and 5-year survival (p<0.001). No association was found between tumour necrosis and signalling markers of the IL-6/JAK/ STAT and NF-KB pathways. On univariate survival analysis age (p<0.001), ASA (p<0.001), T-stage (p<0.001), N-stage (p<0.001), tumour budding (p<0.05), venous invasion (p<0.01), adjuvant therapy (p<0.01), margin involvement (p<0.001), necrosis (p<0.01), SIG (p<0.001), MUST (p<0.001), BMI (p<0.05), sub cutaneous obesity (p<0.001), visceral obesity (p<0.05), Sarcopenia (Martin, p<0.05), Sarcopenia (Dolan, p<0.01), Myosteatosis (Dolan, p<0.05) GMS (p<0.001), Ki67 (p<0.01) and TSP (p<0.01) were independently associated with overall survival. Conclusion There is a clear association between tumour necrosis, the SIR and body composition in patients with colon cancer. These results are consistent with the hypothesis that tumour necrosis and the subsequent inflammatory response results in profound changes in body composition.