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      Systemic immune-inflammation index predicts the clinical outcome in patients with metastatic renal cell cancer treated with sunitinib

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          Abstract

          Background

          In this retrospective analysis, we explored the prognostic and predictive value of the systemic immune-inflammation index (SII), based on lymphocyte, neutrophil, and platelet counts, at baseline and changes at week 6 during first-line sunitinib in patients with metastatic renal cell cancer (RCC).

          Results

          Patients were stratified into high SII (≥ 730) and low SII (< 730) groups. SII was associated with objective response, p < 0.0001. The median PFS was 6.3 months (95% CI 5.5–8.9) in patients with SII ≥ 730 and 18.7 months (95% CI 14.7–22.8) in those with SII < 730, p < 0.0001. The median OS was 43.6 months (95% CI 35.3–52.1) in patients with SII < 730, and 13.5 months (95% CI 9.8–18.5) in those with SII ≥ 730, p < 0.0001. In multivariate analysis, performance status, IMDC score and SII were able to predict OS (HR = 3.29, HR = 1.71 and HR = 1.79, respectively).

          Materials and Methods

          We included 335 consecutive RCC patients treated with first-line sunitinib. The X-tile 3.6.1 software (Yale University, New Haven, CT) was used for bioinformatic analysis of the data to determine the cutoff value of SII. Progression-free survival (PFS), overall survival (OS) and their 95% confidence interval (95% CI) were estimated by Kaplan-Meier method and compared with logrank test. The impact of SII conversion at week 6 of treatment on PFS and OS was evaluated by Cox regression analyses.

          Conclusions

          The SII and its changes during treatment represent a powerful prognostic indicator of clinical outcome in patients with metastatic RCC.

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          Most cited references16

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          Prognostic factors for overall survival in patients with metastatic renal cell carcinoma treated with vascular endothelial growth factor-targeted agents: results from a large, multicenter study.

          There are no robust data on prognostic factors for overall survival (OS) in patients with metastatic renal cell carcinoma (RCC) treated with vascular endothelial growth factor (VEGF) -targeted therapy. Baseline characteristics and outcomes on 645 patients with anti-VEGF therapy-naïve metastatic RCC were collected from three US and four Canadian cancer centers. Cox proportional hazards regression, followed by bootstrap validation, was used to identify independent prognostic factors for OS. The median OS for the whole cohort was 22 months (95% CI, 20.2 to 26.5 months), and the median follow-up was 24.5 months. Overall, 396, 200, and 49 patients were treated with sunitinib, sorafenib, and bevacizumab, respectively. Four of the five adverse prognostic factors according to the Memorial Sloan-Kettering Cancer Center (MSKCC) were independent predictors of short survival: hemoglobin less than the lower limit of normal (P < .0001), corrected calcium greater than the upper limit of normal (ULN; P = .0006), Karnofsky performance status less than 80% (P < .0001), and time from diagnosis to treatment of less than 1 year (P = .01). In addition, neutrophils greater than the ULN (P < .0001) and platelets greater than the ULN (P = .01) were independent adverse prognostic factors. Patients were segregated into three risk categories: the favorable-risk group (no prognostic factors; n = 133), in which median OS (mOS) was not reached and 2-year OS (2y OS) was 75%; the intermediate-risk group (one or two prognostic factors; n = 301), in which mOS was 27 months and 2y OS was 53%; and the poor-risk group (three to six prognostic factors; n = 152), in which mOS was 8.8 months and 2y OS was 7% (log-rank P < .0001). The C-index was 0.73. This model validates components of the MSKCC model with the addition of platelet and neutrophil counts and can be incorporated into patient care and into clinical trials that use VEGF-targeted agents.
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            High blood neutrophil-to-lymphocyte ratio is an indicator of poor prognosis in malignant mesothelioma patients undergoing systemic therapy.

            Asbestos-induced chronic inflammation is implicated in the pathogenesis of malignant mesothelioma (MM). We have investigated blood neutrophil-to-lymphocyte ratio (NLR), an index of systemic inflammation, as a prognostic factor in MM patients. Patients with MM who had systemic therapy at participating institutes were studied. Potential prognostic factors such as age, gender, performance status, histologic subtype, and baseline laboratory parameters, including NLR, were analyzed. Overall survival from commencement of therapy was determined by the Kaplan-Meier method. Multivariate analyses using Cox Regression model were performed with significant factors (P ≤ 0.05) to determine their independent effect. A total of 173 MM patients undergoing systemic therapy including 119 patients receiving first-line therapy and 54 patients receiving second- or third-line therapy were included in this retrospective evaluation. Forty-two percent of patients had an elevated NLR at baseline. The following variables were predictive of survival: female gender (P = 0.044), epithelioid histologic subtype (P < 0.001), baseline white blood cell count less than 8.3 × 10⁹/L (P = 0.008), baseline platelet count 400 × 10⁹/L or less (P = 0.05), and NLR of 5 or less (P < 0.001). After multivariate analysis, histologic epithelioid subtype [hazard ratio (HR) = 2.0; 95% confidence interval (CI) = 1.3-2.9; P = 0.001], and NLR less than 5 (HR = 2.7; 95% CI = 1.8-3.9; P < 0.001) remained independent predictors. The 1-year survival rate was 60% versus 26%, whereas the 2-year survival rate was 34% versus 10% for NLR less than 5 and 5 or greater, respectively. In the separate analyses of chemotherapy-naive and previously treated patient groups, NLR was an independent predictor of survival in both groups. Our results indicate that NLR is an independent predictor of survival for patients with MM undergoing systemic therapy. ©2010 AACR.
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              Blood neutrophil-to-lymphocyte ratio predicts survival in patients with colorectal liver metastases treated with systemic chemotherapy.

              Whether neutrophil-to-lymphocyte ratio (NLR) predicts survival of patients with colorectal liver metastases (CLM) treated with systemic chemotherapy remains unclear. Clinicopathologic data were reviewed for patients with CLM treated with chemotherapy and resection (n=200) or chemotherapy only (n=90). Univariate and multivariate analyses for prognostic factors were performed. In the resection group, whether chemotherapy normalizes high NLR and the effect of NLR normalization on survival were evaluated. In the resection group, patients with preoperative NLR>5 had a worse 5-year survival rate than patients with NLR 5 was the only independent preoperative predictor of worse survival (P=0.016; hazard ratio [HR]=2.22; 95% confidence interval [95% CI], 1.16-4.25). In the nonresection group, patients with prechemotherapy NLR>5 had a worse 3-year survival rate than patients with NLR 5 was the only independent predictor of worse survival (P=0.001; HR = 2.91; 95% CI, 1.54-5.50). In the resection group, chemotherapy normalized high NLR in 17 of 25 patients, and these 17 patients had better survival than the 8 patients with high NLR both before chemotherapy and before surgery (P=0.021). NLR independently predicts survival in patients with CLM treated with chemotherapy followed by resection or chemotherapy only. When chemotherapy normalizes high NLR, improved survival is expected.
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                Author and article information

                Journal
                Oncotarget
                Oncotarget
                Oncotarget
                ImpactJ
                Oncotarget
                Impact Journals LLC
                1949-2553
                23 August 2016
                9 July 2016
                : 7
                : 34
                : 54564-54571
                Affiliations
                1 Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy
                2 Medical Oncology Unit 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy
                3 Oncology Unit 2, University Hospital of Pisa, Pisa, Italy
                4 Department of Medical Oncology, Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy
                5 Department of Medical Oncology, Polytechnic University of the Marche Region, Azienda Ospedaliero-Universitaria, Ospedali Riuniti Umberto I-GM Lancisi and G Salesi, Ancona, Italy
                6 Department of Medical Oncology, University Hospital Southampton NHS Foundation Trust, Southampton General Hospital, Southampton, UK
                7 Department of Medical Oncology, IRCCS CROB Centro di Riferimento Oncologico della Basilicata, Rionero in Vulture, Italy
                8 Present address: Division of Oncology, S.Orsola-Malpighi Hospital, Bologna, Italy
                Author notes
                Correspondence to: Ugo De Giorgi, ugo.degiorgi@ 123456irst.emr.it
                Article
                10515
                10.18632/oncotarget.10515
                5342364
                27409344
                2a0df9e8-1274-48ca-b12e-46b2a51badeb
                Copyright: © 2016 Lolli et al.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 April 2016
                : 23 May 2016
                Categories
                Research Paper

                Oncology & Radiotherapy
                systemic immune inflammation index,renal cell carcinoma,rcc,prognostic factor,sunitinib

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