Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality worldwide. Novel markers are required in order to select high-risk patients and better adjust the treatment. Both peripheral and local markers of cancer-related inflammation (CRI) such as lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR) and tumor-infiltrating lymphocytes (TILs) have been thoroughly investigated in recent years and deemed to be highly prognostic. We hypothesized that there is an association between local and peripheral CRI indices and that blood-based biomarkers may serve as a surrogate of TILs. We retrospectively analyzed 87 patients with locally advanced left-sided CRC treated with radical-intent surgery in the Maria Skłodowska-Curie National Research Institute of Oncology in Warsaw, Poland, between January 2014 and December 2015. Fifty patients were found eligible for the study. The patients were divided in terms of pre-treatment values of systemic inflammatory response (SIR) markers into LMR/NLR/PLR-high and low groups. We evaluated the resected specimens by immunohistochemistry in order to assess the densities of CD3+ and CD8+ lymphocytes in the center of the tumor and in the invasive margin. We found that the level of CD3+ lymphocytes in the center of the tumor was statistically significantly higher in patients with low pre-treatment NLR (p = 0.044); however, no correlation between any of the SIR markers and CD3+ or CD8+ TILs was observed. Five-year overall survival (OS) was longer in patients with high LMR (p < 0.001), low NLR (p = 0.001) and low PLR (p = 0.095). No correlation between the density of TILs and OS was demonstrated. In conclusion, based on our study, peripheral blood-based markers and CD3+ and CD8+ TILs are not interrelated.

Rectal cancer constitutes around one-third of all colorectal cancers. New markers are required to optimize the treatment. Extramural vascular invasion (EMVI) is a magnetic resonance imaging (MRI)-based negative prognostic marker. Lymphocyte-to-monocyte ratio (LMR), neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR) are blood-based systemic inflammatory response markers with proven prognostic value in many cancers, including CRC. We hypothesized whether there is a relationship between LMR, NLR, PLR and the presence of EMVI on pre-treatment MRI in patients with locally advanced rectal cancer (LARC). We conducted a retrospective analysis of 371 patients with LARC treated in the Maria Skłodowska-Curie National Research Institute of Oncology, Warsaw, Poland between August 2016 and December 2021. One hundred eighty-four patients were found eligible for the study. A correlation between the extension of the tumour, nodal status, clinical stage of the disease and the presence of EMVI was found (p < 0.001). The pre-treatment level of neutrophils, platelets and carcinoembryonic antigen (CEA) was significantly higher in the EMVI-positive population (p = 0.041, p = 0.01, p = 0.027, respectively). There were no significant differences regarding the level of LMR, NLR and PLR between the EMVI-positive and EMVI-negative population. LMR, NLR and PLR do not differentiate patients in terms of EMVI; neither of these parameters is a good predictor of the status of EMVI in LARC.

715 Background: Lymphocyte-to-monocyte ratio (LMR) is a strong prognostic factor in many cancers. Recently, in Polish-2 study it was demonstrated to have a predictive value for hypofractionated neoadjuvant radiotherapy in rectal cancer (WCGIC 2017). LMR > 2.6 was associated with significant improvement of overall survival after short-course radiotherapy (5x5 Gy) and consolidating chemotherapy when compared to chemoradiotherapy (HR 0.36). To our knowledge this is the first observation on use of a predictive biomarker for hypofractionated radiotherapy. In this study we assessed the intra-patient variability of pre-treatment LMR in order to evaluate its reproducibility. Methods: Patients with rectal cancer treated in Maria Sklodowska-Curie Memorial Cancer Center, Warsaw, Poland between January 2013 and August 2017 were identified. In order to test reproducibility of the biomarker, only the patients with minimum two peripheral blood morphology tests within 5 weeks prior to any anti-cancer therapy were selected. Other inclusion criteria were locally advanced rectal cancer with no distant metastasis; no prior radiotherapy or chemotherapy. Patients with LMR > 2.6 were identified as “LMR high”. Results: After pre-screening of 719 rectal cancer patients, 50 patients met the inclusion criteria. LMRs calculated at two time-points were correlated with the coefficient of 0.588 (p < 0.05). 40% of assessments were “LMR high”. In 18% of patients the second test has not confirmed initial assignment to LMR class (95% CI 8.6%-31.4%). If LMR at the first time-point was in the range of 2.2-3.0 (+/- 0.4 from cut off), the chance for misclassification rose to 40% (95% CI 12.2%-73.8%), while outside of this range it dropped to 7.5% (95% CI 1.6%-20.4%). Conclusions: In our study LMR demonstrated significant intra-patient variability, espetially in patients with LMR outside of the indicated range (2.2-3.0). Further translational research is needed to identify the exact biological context of this biomarker in order to identify the molecular subtype of rectal cancer responding to hypofractionated radiotherapy.

166 Background: Rectal cancer constitutes over one-third of all colorectal cancers (CRC) and is one of the leading cause of cancer-related death in developed countries. Treatment modalities applied in locally advanced tumors differ substantially among research centers. In order to identify high-risk patients and better adjust the therapy new markers are needed. Systemic inflammatory response (SIR) markers such as LMR, NLR and PLR have been proved highly prognostic in many malignancies, including CRC; however, they lack proper validation. In our study we assessed the reproducibility of LMR, NLR and PLR. Methods: Sixty patients with locally advanced rectal cancer treated in Maria-Sklodowska Curie National Institute of Oncology in Warsaw, Poland between 08.2017 and 12.2020 were prospectively enrolled in the study. Three consecutive blood morphology tests of each patient within a median period of 21 days were obtained before start of the treatment. Results: LMR, NLR and PLR calculated at two time-points were correlated with the coefficient of 0.776, 0.696 and 0.751 (p < 0.005 in all measurements), respectively. Patients were divided into LMR, NLR, PLR-high and low groups. If LMR at the first test was out of the range of 2.2-3.0 (+/- 0.4 from the cut-off) the risk of misclassification in the second measurement defined as an affiliation to a different (high or low) group than initially was 5.0% (95% CI 1.0-13.9%). In case of NLR, when outside of the range of 2.5-3.5 (+/- 0.5) it was 8.3% (95% CI 2.8-18.4%) and PLR outside of the range of 125-175 (+/- 25) 10.0% (95% CI 3.8-20.5%). Mean percentage change between the third and the first measurement of lymphocytes, monocytes, neutrophils and platelets count ranged from -5.59% to 4.76% and the standard error from 2.0 to 3.9. Conclusions: In conclusion SIR markers are reproducible, easily obtained biomarkers with potential application in clinical practice.

Rectal cancer constitutes over one-third of all colorectal cancers (CRC) and is one of the leading cause of cancer-related death in developed countries. Treatment modalities applied in locally advanced tumors differ substantially among research centers. In order to identify high-risk patients and better adjust the therapy new markers are needed. Systemic inflammatory response (SIR) markers such as LMR, NLR and PLR have been proved highly prognostic in many malignancies, including CRC; however, they lack proper validation. In our study we assessed the reproducibility of LMR, NLR and PLR. Sixty patients with locally advanced rectal cancer treated in Maria-Sklodowska Curie National Research Institute of Oncology in Warsaw, Poland between 08.2017 and 12.2020 were prospectively enrolled in the study. Three consecutive blood morphology tests of each patient within a median period of 21 days were obtained before start of the treatment. LMR, NLR and PLR calculated at two time-points were correlated with the coefficient of 0.776, 0.696 and 0.751 (p<0.005 in all measurements), respectively. Cohen’s Kappa statistic for the extent of agreement between the 1st and the 2nd measurement for LMR was κ = 0.59 (95% CI, 0.39-0.79), p < 0.001. For NLR the Kappa was κ = 0.45 (95% CI, 0.22-0.68), p < 0.001 and for PLR κ = 0.53 (95% CI, 0.32-0.75. Mean percentage change between the third and the first measurement of lymphocytes, monocytes, neutrophils and platelets count ranged from -5.59–4.76% and the standard error from 2.0 to 3.9. In conclusion, SIR markers are moderately reproducible, easily obtained biomarkers with potential application in clinical practice.