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Clinical significance of tumor-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio in patients with stage III colon cancer who underwent surgery followed by FOLFOX chemotherapy.

ABSTRACT: Local tumor immune response and host immunity have been suggested as important prognosticators respectively in colorectal cancer. However, the utility of combination of these parameters remains inconclusive. The aim of this study was to investigate the combinational impact of local and host tumor immune response, as determined by tumor-infiltrating lymphocytes (TILs) and neutrophil-to-lymphocyte ratio (NLR), in patients with stage III colon cancer. Patients with stage III colon cancer homogeneously treated with surgery followed by FOLFOX chemotherapy between Jan 2007 and Aug 2013 were included retrospectively. Hematoxylin and eosin (H&E) stained tumor sections of local inflammatory infiltrate (TILs) were classified as 0-3 by the Klintrup-Mäkinen grading method. NLR was measured within 1 month of surgery. The association of NLR and TILs with survival, alone or combined, were measured using multivariate Cox proportional hazard regression analysis. Among 137 patients, 75 (54.7%) were identified as the high TIL group (TILs 2 and 3) and 97 (70.8%) as the low NLR group (NLR < 3). Of the patients with high TILs, 51 (68%) had a low NLR. In univariate analysis, operation time, complications, lymph node ratio (LNR), stage, TILs, and high TILs with low NLR were significantly associated with overall survival(OS). Multivariate Cox regression identified operation time, stage, and TILs as independent risk factors for OS. When high TILs with low NLR vs. others was entered into multivariate analysis, this also proved to be a significant predictor of OS (HR 4.1, 95% CI 1.1-14.2, P = 0.025), with an increased C-index and lower AIC value compared to TILs. Measuring TILs using H&E stained sections could stratify the prognosis of stage III colon cancer. Considering host immunity, using the combination of TILs and NLR, allowed the prognosis to be stratified in more detail.

SUBMITTER: Cha YJ

PROVIDER: S-EPMC6690947 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Predicting survival of patients with malignant pleural effusions (MPEs) is notoriously difficult. A robust prognostic marker can guide clinical decision making. The neutrophil-to-lymphocyte ratio (NLR) in blood has been shown to predict survival in many cancers. Pleural fluid bathes the malignant pleural tissues, thus the NLR of the pleural fluid may reflect more closely the local tumour environment. The objective of this study was to explore the prognostic significance of pleural effusion NLR for MPE. We analysed matched effusion and blood from 117 patients with malignant and 24 with benign pleural effusions. Those who had received recent chemotherapy or had a pleurodesis were excluded. Neutrophil and lymphocyte counts in effusions were performed by manual review of cytospin cell preparations by trained observers. Clinical data were extracted from a state-wide hospital database. We found significantly fewer neutrophils (expressed as percentage of total leukocyte count) in pleural fluid than in corresponding blood (9% vs 73%; p<0.001). The NLR was an order of magnitude lower in pleural fluid than in corresponding blood: median [IQR] = 0.20 [0.04-1.18] vs 4.9 [3.0-8.3], p<0.001. Correlation between blood and pleural fluid NLR in MPE patients was moderate (rs = 0.321, p<0.001). In univariate analysis, NLR (>0.745)) in malignant pleural fluid was predictive of poorer survival (HR = 1.698 [1.0054-2.736]; p = 0.030), and remained significant after adjustment for age, sex, presence of a chest drain, cancer type, concurrent infection and subsequent treatment with chemotherapy (HR = 1.786 [1.089-2.928]; p = 0.022). Patients with pleural fluid NLR > 0.745 had a significantly shorter median survival of 130 (95% CI 0-282) days compared to 312 (95% CI 195-428) days for pleural NLR < 0.745, p = 0.026. The NLR in blood was also predictive of poorer survival in MPE patients (HR = 1.959 [1.019-3.096]; p<0.001). The proportion of neutrophils in pleural fluid was predictive of prognosis more strongly than lymphocytes. This study provides evidence that NLR in malignant effusions can predict survival, and therefore may provide prognostic information for this cohort. This prognostic association in the fluid is driven by the presence of neutrophils.

Project description:Elevated neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) may represent markers of a suboptimal host immune response to cancer and have been shown to correlate with prognosis in multiple tumor types across different treatment modalities, including radiation therapy. Limited data suggest that NLR may predict for survival and disease control in patients receiving selective internal radiation therapy (SIRT). The correlation between clinical outcomes and change in NLR and PLR after SIRT has not been evaluated.We retrospectively reviewed 339 consecutive patients with primary (n=37) or metastatic (n=79) liver cancer treated with SIRT from 2006 to 2014. Complete blood counts with differential were available for 116 patients both before and after (median, 29 and 20 days, respectively) SIRT. Survival and progression were calculated from date of initial SIRT. Patient and tumor characteristics evaluated for ability to predict overall survival (OS) and progression free survival (PFS) included pre- and post-treatment neutrophil, platelet, and lymphocyte counts (LCs), as well as NLR, PLR, and relative change in NLR and PLR. Cutoff values were determined for variables that were significant on multivariate analysis (MVA) for OS and/or PFS.Median follow-up of surviving patients was 12 months. Median OS was 8 months from SIRT and 20 months from date of liver metastasis diagnosis. Significant factors on univariate analysis (UVA) for both lower OS and PFS included higher post-treatment neutrophil count (NC), higher post-treatment NLR, higher liver tumor volume, higher percentage liver tumor burden, and worse Eastern Cooperative Oncology Group (ECOG) performance status. Significant factors on MVA for lower OS and PFS were ECOG performance status ?2, higher liver tumor volume, higher pretreatment PLR, and increase in PLR after SIRT. Post-treatment increase in PLR >3-fold was the most predictive early marker for increased risk of death when compared with those whose PLR did not increase or increased <3-fold. Pretreatment PLR >78 was the most predictive serum marker associated with improved OS prior to therapy.This is the largest study to evaluate the association between NLR and PLR with clinical outcomes in patients receiving SIRT, with results that confirm that pre- and/or post-treatment NLR and/or PLR are predictive of clinical outcomes. The largest increase in risk of death as well as local and extrahepatic disease progression was related to change in PLR, a datum not well reported in the literature. The impact of SIRT on blood count changes and the underlying implications of these ratios should be further characterized in a prospective study.

Project description:AimNeutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), or monocyte-lymphocyte ratio (MLR) has been shown to be related to the poor prognosis of cervical cancer, ovarian cancer, breast cancer, and other malignant tumors, but their role in predicting the prognosis of endometrial cancer is still controversial. Therefore, we conducted this meta-analysis to evaluate the effectiveness of NLR more accurately, PLR, or MLR in predicting the prognosis of endometrial cancer (EC).MethodsThis review systematically searched for relevant publications in databases of the Cochrane Library, PubMed, EMBASE, CNKI, WanFang, VIP, and CBM. Pooled hazard ratios (HR) with 95% confidence intervals (95% CI) were determined and used to explore the association between inflammatory biomarkers (NLR, PLR, and MLR) and overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS) in a random-effects model. We also conducted subgroup analysis and publication bias in this meta-analysis. Stata 12.0 was used for statistical analysis.ResultsThis meta-analysis contained 14 eligible studies including 5,274 patients. Our results showed that NLR or PLR was associated with OS [NLR: HR, 2.51; 95% CI, 1.70-3.71; p <0.001 in univariate analysis (Ua); HR, 1.87; 95% CI, 1.34-2.60; p <0.001 in multivariate analysis (Ma); PLR: HR, 2.50; 95% CI, 1.82-3.43; p <0.001 in Ua; HR, 1.86; 95% CI, 1.22-2.83; p = 0.004 in Ma], but MLR was not associated with OS (HR, 1.44; 95% CI, 0.70-2.95; p = 0.325 in Ua; HR, 1.01; 95% CI, 0.39-2.60; p =0.987 in Ma). A further subgroup analysis found that the correlations were not affected by race, cutoff value, sample size, or treatment. Our meta-analysis showed that NLR or PLR was associated with DFS (NLR: HR, 2.50; 95% CI, 1.38-4.56; p =0.003 in Ua; HR, 2.06; 95% CI, 1.26-3.37, P =0.004 in Ma; PLR: HR, 1.91; 95% CI, 1.30-2.81; p = 0.001 in Ua), and NLR was associated with PFS only in the univariate analysis (HR, 1.71; 95% CI, 1.04-2.81; p =0.035 in Ua; HR, 1.79; 95% CI, 0.65-4.89; P =0.257 in Ma), but MLR was not associated with DFS (HR, 0.36; 95% CI, 0.03-4.13; p =0.409 in Ua).ConclusionsOur results indicated that pretreatment NLR and PLR were biomarkers of poor prognosis in patients with endometrial cancer. The results indicated that NLR or PLR was associated with OS and disease-free survival DFS, and NLR was associated with PFS only in univariate analysis, but MLR was not associated with OS or DFS.

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Clinical significance of tumor-infiltrating lymphocytes and neutrophil-to-lymphocyte ratio in patients with stage III colon cancer who underwent surgery followed by FOLFOX chemotherapy.

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