Neutrophil-to-lymphocyte ratio (NLR) as an independent prognostic marker in MUTYH- associated colorectal cancers (MUTYH-CRCs).

e15719 Background: MUTYH-associated polyposis (MAP) is a hereditary colorectal cancer (CRC) syndrome caused by biallelic mutations in the MUTYH gene. Unlike sporadic CRC, MAP tumors exhibit a unique molecular profile, characterized by oxidative DNA damage and subsequent mutagenesis. Identification of reliable prognostic markers for MUTYH-CRCs is essential for personalized treatment strategies. The neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has gained recognition as a prognostic indicator in several malignancies that reflects the balance between the inflammatory and immune responses. However, its role in MUTYH-associated CRC remains poorly understood. Methods: Clinical data were obtained from patients with MUTYH-CRCs who presented to Moffitt Cancer Center (Tampa, FL) between 2015 and 2023. Selected variables included in the multivariate (MV) analyses were log2 (NLR1or 2), smoking, sex, and stage. NLR was calculated by dividing the absolute neutrophil count by the lymphocyte count at baseline (NLR 1) and during treatment (30 days after treatment initiation NLLR 2). Patients were stratified into 2 groups; NLR-high (H: > 3) or low (L; < 3). Time-to-event endpoints were evaluated to assess survival and response at the initiation of treatment using the Kaplan Meier and Cox Proportional Hazards Models. Results: A total of 36 patients with MUTYH-CRCs were identified. Demographic and baseline characteristics were similar between the two groups. High levels of NLR1 were observed in 42 % of the patients and were significantly associated with advanced tumor stage (P < 0.01) and the presence of lymphovascular invasion (P = 0.02). High levels of NLR2 were detected in 28 % of the patients and were associated with poor overall survival (OS) (HR: 2.15; 95% CI: 1.45-3.12) and disease- free survival (DFS) (HR: 1.92; 95% CI: 1.33-2.78). Multivariate analysis confirmed that NLR was an independent prognostic factor for both OS (adjusted HR: 1.88; 95% CI: 1.21–2.94) and DFS (adjusted HR: 1.73; 95% CI: 1.12–2.66), independent of tumor stage or molecular characteristics. Conclusions: NLR is an independent prognostic marker in MUTYH-CRCs. A high NLR at time of diagnosis is associated with advanced tumor stage and the presence of lymphovascular invasion. A high NLR within 30 days of treatment is associated with worse OS and DFS. Further studies in larger cohorts are warranted to explore the mechanistic links between systemic inflammation and MUTYH- associated tumor biology.