Background:The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response. Previous findings from small-scale studies revealed conflicting results about its independent prognostic significance with regard to different clinical end points in pancreatic cancer (PC) patients. Therefore, the aim of our study was the external validation of the prognostic significance of NLR in a large cohort of PC patients.Methods:Data from 371 consecutive PC patients, treated between 2004 and 2010 at a single centre, were evaluated retrospectively. The whole cohort was stratified into two groups according to the treatment modality. Group 1 comprised 261 patients with inoperable PC at diagnosis and group 2 comprised 110 patients with surgically resected PC. Cancer-specific survival (CSS) was assessed using the Kaplan–Meier method. To evaluate the independent prognostic significance of the NLR, the modified Glasgow prognostic score (mGPS) and the platelet-lymphocyte ratio univariate and multivariate Cox regression models were applied.Results:Multivariate analysis identified increased NLR as an independent prognostic factor for inoperable PC patients (hazard ratio (HR)=2.53, confidence interval (CI)=1.64–3.91, P<0.001) and surgically resected PC patients (HR=1.61, CI=1.02–2.53, P=0.039). In inoperable PC patients, the mGPS was associated with poor CSS only in univariate analysis (HR=1.44, CI=1.04–1.98).Conclusion:Risk prediction for cancer-related end points using NLR does add independent prognostic information to other well-established prognostic factors in patients with PC, regardless of the undergoing therapeutic modality. Thus, the NLR should be considered for future individual risk assessment in patients with PC.
Background: Inflammation has a critical role in the pathogenesis and progression of cancer. The lymphocyte to monocyte ratio (LMR) could be shown to be prognostic in haematologic neoplasia. In this study, we analysed the LMR with clinical outcome in stage II and III colon cancer patients.
Tertiary lymphoid structures (TLS) are associated with favorable outcome in non-metastatic colorectal carcinoma (nmCRC), but the dynamics of TLS maturation and its association with effective anti-tumor immune surveillance in nmCRC are unclear. Here, we hypothesized that not only the number of TLS but also their composition harbors information on recurrence risk in nmCRC. In a comprehensive molecular, tissue, laboratory, and clinical analysis of 109 patients with stage II/III nmCRC, we assessed TLS numbers and degree of maturation in surgical specimens by multi-parameter immunofluorescence of follicular dendritic cell (FDC) and germinal center (GC) markers. TLS formed in most tumors and were significantly more prevalent in highly-microsatellite-instable (MSI-H) and/or BRAF-mutant nmCRC. We could distinguish three sequential TLS maturation stages which were characterized by increasing prevalence of FDCs and mature B-cells: [1] Early TLS, composed of dense lymphocytic aggregates without FDCs, [2] Primary follicle-like TLS, having FDCs but no GC reaction, and [3] Secondary follicle-like TLS, having an active GC reaction. A simple integrated TLS immunoscore reflecting these parameters identified a large subgroup of nmCRC patients with a very low risk of recurrence independently of clinical co-variables such as ECOG performance status, age, stage, and adjuvant chemotherapy. We conclude that (1) mismatch repair and BRAF mutation status are associated with the formation of TLS in nmCRC, (2) TLS formation in nmCRC follows sequential maturation steps, culminating in germinal center formation, and (3) this maturation process harbors important prognostic information on the risk of disease recurrence.
Background:Inflammation has a critical role in the pathogenesis and progression of cancer. Recently, the derived neutrophil to lymphocyte ratio (absolute count of neutrophils divided by the absolute white cell count minus the absolute count of neutrophils; dNLR) has been shown to influence clinical outcome in various cancer entities. In this study, we analysed the dNLR with clinical outcome in stage II and III colon cancer patients.Methods:Three-hundred and seventy-two patients with stage II and III colon cancer were included in this retrospective study. Kaplan–Meier curves and multivariate Cox proportion analyses were calculated for time to recurrence (TTR) and overall survival (OS).Results:In univariate analysis, the elevated preoperative dNLR was significantly associated with decreased TTR (hazard ratio (HR) 2.38, 95% confidence interval (CI) 1.57–3.6, P<0.001) and remained significant in multivariate analysis. Patients with dNLR >3 had a median TTR of 83 months, and patients with dNLR ⩽3 showed a median TTR of 132 months. In OS analysis, a dNLR >2.2 was significantly associated with decreased OS in univariate (HR 1.85, 95% CI 1.11–3.08, P=0.018) and multivariate analysis. Patients with dNLR >2.2 showed a median OS of 121 months, and patients with dNLR ⩽2.2 had a median OS of 147 months.Conclusion:The dNLR may be an independent prognostic marker for TTR and OS in patients with stage II and III colon cancer. Independent validation of our findings is warranted.
Increasing evidence indicates the involvement of inflammation and coagulation in cancer progression and metastases. Inflammatory biomarkers hold great promise for improving the predictive ability of existing prognostic tools in cancer patients. In the present study, we investigated several inflammatory indices with regard to their prognostic relevance for predicting clinical outcome in soft tissue sarcoma (STS) patients. Three hundred and forty STS patients were divided into a training set (n 5 170) and a validation set (n 5 170). Besides well-established clinico-pathological prognostic factors, we evaluated the prognostic value of the neutrophil/lymphocyte (N/L) ratio, the lymphocyte/monocyte (L/M) ratio and the platelet/lymphocyte (P/L) ratio using Kaplan-Meier curves and univariate as well as multivariate Cox regression models. Additionally, we developed a nomogram by supplementing the L/M ratio to the well-established Kattan nomogram and evaluated the predictive accuracy of this novel nomogram by applying calibration and Harrell's concordance index (c-index). In multivariate analysis, a low L/M ratio was significantly associated with decreased CSS and DFS (HR 5 0.41, 95% CI 5 0.18-0.97, p 5 0.043; HR 5 0.39, 95% CI 5 0.16-0.91, p 5 0.031, respectively) in the training set. Using the validation set for confirmation, we found also in multivariate analysis an independent value for CSS (HR 5 0.33, 95% CI 5 0.12-0.90, p 5 0.03) and for DFS (HR 5 0.36, 95% CI 5 0.16-0.79, p 5 0.01). The estimated c-index was 0.74 using the original Kattan nomogram and 0.78 when the L/M ratio was added. Our study reports for the first time that the pre-operative L/M ratio represents a novel independent prognostic factor for prediction the clinical outcome in STS patients. This easily determinable biomarker might be helpful in improved individual risk assessment.Soft tissue sarcomas (STS) account for nearly 11,280 cases per year and are responsible for about 3,900 deaths in the United States annually, mainly due to local recurrence or metastatic disease. 1 Therefore, it is crucial to understand the biological mechanisms that contribute to tumor progression and to identify novel prognostic markers to generate individualized treatment and follow-up schedules. In a large retrospective study of 2,136 STS patients, Kattan et al. developed a postoperative prognostic model that predicts sarcomaspecific death, based on traditional prognostic factors such as age at diagnosis, tumor size, histologic grade, histologic subtype, tumor depth and site. 2 This nomogram is useful for general risk assessment and has potential value in determining surgical strategy and adjuvant management. Nevertheless, novel prognostic factors might be helpful in improving its predictive ability. Current approaches in cancer research have focused on the characterization of novel biomarkers, which ideally should be easily accessible, highly reproducible, cheap and most importantly, identify patients at high risk for disease-recurrence and death. Increasing evidence su...
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