Prognostic Role Of Macrophage Infiltration And Monocyte-To-Lymphocyte Ratio In Stage Iii Colon Cancer: The Mirror Study.

e16118 Background: Changes in peripheral blood cells composition may reflect immune microenvironment and its role in cancer growth. High monocyte-to-lymphocyte ratio (MLR) could be a marker of tumor’s recruitment of suppressive cells, showing a prognostic role. This study aimed to assess the prognostic impact of macrophage infiltration and MLR in stage III colon cancer (CC) patients (pts). Methods: This multicentric study retrospectively analyzed a consecutive cohort of 423 CC pts treated between 2008-2019 at the Cancer Centre of Aviano (Italy) (n = 300) and at the European Georges Pompidou Hospital of Paris (France) (n = 123). The association of MLR with disease-free survival (DFS) and overall survival (OS) was evaluated with Cox regression analyses. Random Forrest was implemented on python using h2oai. Performance was assessed in terms of accuracy (ACC) and Matthews Coefficient (MCC). Analyses was adjusted on classical prognostic factors of stage III CC such as pT, pN, grade, location, ECOG PS. Results: Overall, 77% had pT1-3, 30% pN2 and 73% G1-2 tumors. Interestingly, 25% had a lymphatic and vascular invasion, 42/230 (18%) had MSI status, 69/152(45%) and 19/114 (13%) were KRAS and BRAF mutant. 56% had CEA > 5. Pts were treated with fluoropyrimidine and oxaliplatin as adjuvant therapy. Notably, 130 cases were analyzed according to lymphocytic and macrophage infiltration (CD163, CD68, CD3, CD8). Of them, 78% had a CD163/CD8 ratio ≤3 and 74% a CD8/CD3 ratio ≤1.5. At median follow-up of 57 months, median DFS and OS were not reached, 31% of pts relapsed and 23% dead. By multivariate analysis, including statistically significant prognostic variables, CD163/CD8 ratio (HR 1.15, p = 0.039, 95%C.I. 1.1-1.32) and MLR > 0.45 (HR 2.98, p = 0.008, 95%C.I. 1.33-6.67) were associated with worse DFS. By multivariate analysis for OS, including statistically significant confounding variables, MLR > 0.45 (HR4.32, P = 0.012, 95%C.I. 1.37-9) and BRAF mutation predicted worse OS. According random survival forest for OS, CD68/CD3 were the first variable of importance (0.06), followed by MLR (0.009) and CD8 (0.007). Interestingly, high MLR followed by CEA, MSI, KRAS were the features linked with organotropism on liver (ACC 0.6 ±0.3), while high MLR, KRAS, pN, pT were mainly linked with lung colonization (ACC 0.6 ±0.2). Conclusions: High pre-treatment levels of MLR and CD163/CD8 ratio in stage III CC are independently associated with worse prognosis. The present study paves the way to a prospective validation of these promising cost-effective biomarkers.