Abstract 416P
Background
Circulating monocytes are recruited in the tumor site where they differentiate into tumor-associated macrophages, acquiring pro-tumor functions and suppressing adaptive immune response. This study aims to investigate a prognostic tool based on lymphocytes ratio (LR) in patients (pts) with stage III colon cancer (CC).
Methods
This is a multicentric study conducted on 653 consecutive CC pts treated between 2008-2019 at the Centres of Aviano, Pordenone, Udine and Paris (HEGP). A Cox regression model was used to determine the prognostic impact in terms of overall survival (OS) and disease-free survival (DFS). The performance of the prognostic model was evaluated using the Harrell’s C statistic (HCS). Random Forest (RF) to predict pattern of metastasis was implemented on python using H2oai.
Results
Overall, 70% of pts had stage IIIB, 75% G1-2 tumors and 57% CEA>5. Notably, 50%, 41% and 14% had a lymphatic (LI), vascular (VI) and perinervouse infiltration (PI), respectively. About molecular profile, 45/263 had MSI status, 94/212 and 28/199 were KRAS and BRAF muted. At median follow-up of 59 mo, median DFS and OS were not reached, 32% of pts relapsed and 24% died. At 3-year follow-up, 24% had a DFS event. By multivariate analysis, including potential confounders, significantly shorter DFS (HR 1.84, 95%CI 1.13-3.00, p=0.014) and OS (HR 2.32, 95%CI 1.27-4.25) were observed among pts with high monocyte-to-LR (MLR >0.45) compared to those with low MLR. Notably, MLR was significantly associated with 3y-DFS (p=0.02). The addition of MLR improved the performance of the prognostic model (from 0.69 to 0.87 HCS). RF showed that BRAF, LR, sidedness, KRAS, CEA, and LDH were the main features linked with hepatic (ACC 0.67) and nodal (0.68) organotropism. LDH, PI, LR, KRAS, pT, pN with lung (0.77), while LR, sidedness, KRAS, BRAF, MMR and VI with bone involvement (ACC 0.55). Factors linked with peritoneal involvement were LR, CEA, BRAF, pT, pN (ACC 0.57).
Conclusions
A prognostic model including MLR results more accurate in predicting survival and pattern of metastatic spread in patients with stage III CC, allowing a more tailored monitoring. These findings paved the way at constructing a potential nomogram based on MLR and macrophages immune-score to more accurately define stage III CC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Gallois: Travel/Accommodation/Expenses: Amgen; Honoraria (self): Sanofi; Honoraria (self): Servier. A. Zaanan: Honoraria (self), Research grant/Funding (institution), Travel/Accommodation/Expenses: Amgen; Honoraria (self), Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Baxter; Honoraria (self), Advisory/Consultancy: Merck Serono; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (self), Advisory/Consultancy: Servier; Honoraria (self), Advisory/Consultancy: Sanofi; Honoraria (self), Advisory/Consultancy: Lilly; Travel/Accommodation/Expenses: Merck. G. Fasola: Honoraria (self), Travel/Accommodation/Expenses: Bristol-Myers Squibb S.r.l.; Honoraria (self), Travel/Accommodation/Expenses: ELi Lilly S.p.A.;; Honoraria (self), Travel/Accommodation/Expenses: Servier Italia S.p.A.; Honoraria (self), Travel/Accommodation/Expenses: Astra Zeneca . G. Aprile: Advisory/Consultancy: Amgen; Advisory/Consultancy: Baxter; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Sanofi; Advisory/Consultancy: Servier. J. Taieb: Speaker Bureau/Expert testimony: Roche ; Speaker Bureau/Expert testimony: Merck; Speaker Bureau/Expert testimony: Amgen; Speaker Bureau/Expert testimony: Celgene; Speaker Bureau/Expert testimony: Servier; Speaker Bureau/Expert testimony: MSD; Speaker Bureau/Expert testimony: Sanofi; Speaker Bureau/Expert testimony: Lilly; Speaker Bureau/Expert testimony: Pierre Fabre. F. Puglisi: Honoraria (self): MSD; Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self): Takeda; Honoraria (self): Pfizer; Honoraria (self): Amgen; Advisory/Consultancy: Novartis; Advisory/Consultancy: Pierre Fabre; Advisory/Consultancy: Astra Zeneca; Advisory/Consultancy: Eisai; Travel/Accommodation/Expenses: Celgene; Travel/Accommodation/Expenses: Servier. All other authors have declared no conflicts of interest.