The SAFFO study: Sex-related prognostic role and cut-oFf deFinition of monocyte-to-lymphocyte ratio (MLR) in metastatic colOrectal cancer

Abstract

Background: Emerging data suggest that sex-related immune system composition affect both immune response and efficacy of immunotherapy in cancer patients (pts). This study aimed to investigate the sex-related prognostic role of MLR in metastatic colorectal cancer (mCRC) pts. Methods: We analyzed a retrospective consecutive cohort of 490 mCRC pts treated in 2004-2017 at the Oncology Departments of Aviano and Pordenone (training set) and Udine (validation set), Italy. Association analysis was explored by Chi-squared or Kruskal-Wallis test, as appropriate. The prognostic impact of MLR on overall survival (OS) was evaluated with uni- and multivariable Cox regression models. The best cutoff value to predict survival was defined through ROC analyses. Results: Overall, we identified 288 males and 202 females; 161 pts (33%) had a right cancer and 324 (67%) a left one. Interestingly, sex was associated with MLR (p=0.004). The obtained cut-off value for MLR in females and males was 0.27 and 0.49, respectively. At univariate analysis of training set, MLR >0.27 in females (HR 1.95, p=0.003) and MLR >0.49 in males (HR 2.65, p=0.010) were associated with poorer OS. Even in the validation set, MLR >0.27 in females (HR 2.21, p=0.010) and MLR>0.49 in males (HR 2.99, p=0.002) were associated with shorter OS. In the overall cohort, at univariate analysis MLR >0.27 in females (HR 2.07, p≤0.001), MLR >0.49 in males (HR 2.87, p≤0.001), KRAS mutation (HR 1.37 p=0.008), BRAF mutation (HR 1.69 p=0.009), sidedness (right vs left HR 1.59, p≤0.001) and peritoneal metastases (HR 2.32, p≤0.001) were associated with shorter OS. Instead, primary tumor resection (HR 0.37 p≤0.001) was associated with prolonged OS. At multivariate analysis, MLR>0.27 in females (HR 2.77, p=0.002), MLR>0.49 in males (HR 5.39, p≤0.001), BRAF mutation (HR 3.38, p≤0.001) and peritoneal metastases (HR 2.50, p=0.003) were still independently associated with worse OS. Noteworthy, high MLR was more frequently found in females than in males (41% vs 9%). Conclusions: Males and females have a different immune response. Our study showed that high MLR, both in males and females, is an unfavorable independent prognostic factor. Further prospective studies are needed to confirm these data.