582P - Prognostic role of macrophage infiltration and monocyte-to-lymphocyte ratio in stage III colon cancer: The MIRROR study

Background

Changes in the composition of peripheral blood cells may reflect immune microenvironment and its role in controlling cancer growth. A high monocyte-to-lymphocyte ratio (MLR) could indicate a tumor’s recruitment of suppressive cells. This study aimed to assess the prognostic impact of MLR in stage III colon cancer (CC).

Methods

The multicentric MIRROR study retrospectively analyzed a cohort of 1003 consecutive CC patients treated between 2008-2019 in 4 Italian and French Centers. The associations between MLR and survival outcomes (DFS, RFS and OS) were evaluated with Cox regression analyses.

Results

At a mFU of 53 months, mDFS was 13mo, while mRFS and mOS were not reached. Thirty percent of pts relapsed and 21% died. Moreover, 16%, 67%, and 15% had IIIA, IIIB and IIIC CC, respectively. An MLR>0.46 (identified with ROC curve) predicted worse outcome in both univariable and multivariable models in terms of DFS (HR 1.70, p=0.03), RFS (HR 1.81, P=0.019), and OS (HR 1.80, p=0.014), including confounding variables. Data about the multivariable prognostic model for DFS was confirmed in both the test and training set of the bootstrap resampling method. Finally, MLR, CEA, stage, and age were used in a final nomogram scoring model. We classified patients into high, intermediate, and low nomogram groups, determining an impact on DFS (HR 2.27, p<0.001 intermediate vs. low; HR 3.88, p<0.001 high vs. low), RFS (HR 2.08, p<0.001 intermediate vs. low; HR 3.61, p<0.001 high vs. low), and OS (HR was 2.14, p=0.001 intermediate vs. low, HR 3.96, p<0.001 high vs. low). Notably, an early reduction in MLR within the first 4 month of therapy was associated with a better prognosis in multivariate analysis (HR for DFS HR 0.56, p=0.008; HR for RFS 0.56, p=0.012). Additionally, 103 cases were analyzed for macrophage infiltration. By multivariable analysis, CD163+/CD68+CT (HR 2.34, p=0.06) and stage (IIIC vs. IIIA, HR 3.44, p=0.032) were independently associated with shorter DFS.

Conclusions

High pre-treatment levels of MLR, early MLR reduction, and CD163+/CD68+CT in stage III CC are independent prognostic factors in stage III CC pts. This study paves the way for prospective validation of these promising, cost-effective biomarkers.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

C. Gallois: Financial Interests, Institutional, Invited Speaker: Sanofi Genzyme; Financial Interests, Institutional, Advisory Board: Servier, Pierre Fabre, Merck; Financial Interests, Institutional, Other, French Congress invitation: MSD; Financial Interests, Institutional, Other, Congress invitation: Amgen. J. Taieb: Financial Interests, Personal, Advisory Board: MSD, Astellas, Merck, Servier, Pierre Fabre, Amgen, BMS, Novartis, Pfizer, Sanofi, Rottapharm, Takeda; Financial Interests, Personal, Invited Speaker: Amgen, BMS, Merck, MSD, Novartis; Financial Interests, Personal, Invited Speaker, symposia: Astellas; Financial Interests, Personal, Other, Steering Committee of clinical trial: Novartis; Non-Financial Interests, Leadership Role, President of the scientific committee of the ARCAD foundation until end 2022: ARCAD Foundation; Non-Financial Interests, Leadership Role, Chair of the ARCAD pancreas research group: ARCAD Foundation; Non-Financial Interests, Leadership Role, Member of the administrative council, the scientific committee, the executive board and responsible for the international relationships /partnership for FFCD in the prodige intergroup: Federation Francophone de Cancerologie Digestive (FFCD); Non-Financial Interests, Other, Steering Committee of clinical trials: Pfizer, Servier. All other authors have declared no conflicts of interest.