5416 - The SAFFO study: Sex-related prognostic role And cut-oFf deFinition of monocyte-to-lymphocyte ratio (MLR) in metastatic colOrectal cancer

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 cut-off 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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

IRCCS CRO National Cancer Institute, Aviano, Italy.

Funding

Has not received any funding.

Disclosure

F. Puglisi: Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Hoffmann-La Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Amgen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eisai; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eli Lilly; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Ipsen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Pierre-Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Takeda; Advisory / Consultancy: Merck Sharp & Dohme. All other authors have declared no conflicts of interest.